Submissions for variant NM_000059.4(BRCA2):c.658_659del (p.Val220fs)

dbSNP: rs80359604

Total submissions: 52

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000031637	SCV000282430	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2016-04-22	reviewed by expert panel	curation	Variant allele predicted to encode a truncated non-functional protein.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000044988	SCV000073001	pathogenic	Hereditary breast ovarian cancer syndrome	2024-01-29	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Val220Ilefs*4) in the BRCA2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). This variant is present in population databases (rs768580992, gnomAD 0.01%). This premature translational stop signal has been observed in individual(s) with hereditary breast and ovarian cancer (PMID: 9667259, 22923021, 23767878, 24504028, 26657402). This variant is also known as 886delGT. ClinVar contains an entry for this variant (Variation ID: 9342). For these reasons, this variant has been classified as Pathogenic.
GeneDx	RCV000074548	SCV000108633	pathogenic	not provided	2020-03-16	criteria provided, single submitter	clinical testing	Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Observed in the heterozygous state in individuals from hereditary breast and ovarian cancer families (Frank 1998, Jakubowska 2003, Machado 2007, Berzina 2013, Cunningham 2014, de Juan 2015); Observed in the compound heterozygous state with a second pathogenic BRCA2 variant in patients with Fanconi anemia (Alter 2007, Miele 2015); Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; Also known as 886delGT; This variant is associated with the following publications: (PMID: 9667259, 14647210, 15689453, 27836010, 26681312, 30128899, 17513806, 23767878, 24504028, 26026974, 16825431, 26064523, 26779294, 24528374, 26843898, 22535016, 27376475, 27153395, 26657402, 27831900, 14559878, 14670928, 28724667, 28324225, 28166811, 22009639, 29339979, 29753700, 29492181, 30078507, 29310832, 30350268, 30630528, 30122538, 30720243, 29790872, 29575201, 30093976, 31411802, 31396961, 31263054, 31957001, 27741520, 29625052, 26689913, 32318955, 31447099, 31980526, 31948886, 34008015, 32467295, 31589614, 32341426, 31825140, 32719484, 30787465)
Ambry Genetics	RCV000131858	SCV000186913	pathogenic	Hereditary cancer-predisposing syndrome	2021-11-17	criteria provided, single submitter	clinical testing	The c.658_659delGT pathogenic mutation, located in coding exon 7 of the BRCA2 gene, results from a deletion of 2 nucleotides at positions 658 to 659, causing a translational frameshift with a predicted alternate stop codon (p.V220Ifs*4). This mutation has been described in numerous HBOC families (Frank TS et al. J. Clin. Oncol. 1998 Jul;16:2417-25; Berzina D et al. BMC Med. Genet. 2013;14:61; Meisel C et al. Arch. Gynecol. Obstet. 2017 May;295:1227-1238). This mutation has also been observed in Fanconi anemia group D1 patients and was associated with brain tumors (medulloblastomas and glioblastomas) and Wilms tumor in these patients (Alter BP et al. J. Med. Genet. 2007 Jan;44:1-9; Miele E et al. Biomark Res. 2015;3:13). Of note, this alteration is also designated as 886delGT in some published literature. In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is classified as a disease-causing mutation. However, because this variant is identified in one or more patients with Fanconi Anemia it may be hypomorphic and thus, carriers of this variant and their families may present with reduced risks, and not with the typical clinical characteristics of a high-risk pathogenic BRCA2 alteration. As risk estimates are unknown at this time, clinical correlation is advised.
Michigan Medical Genetics Laboratories, University of Michigan	RCV000031637	SCV000195951	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2014-11-03	criteria provided, single submitter	clinical testing
Counsyl	RCV000031637	SCV000221117	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2015-02-04	criteria provided, single submitter	literature only
University of Washington Department of Laboratory Medicine, University of Washington	RCV000210073	SCV000266043	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2015-11-20	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000131858	SCV000292146	pathogenic	Hereditary cancer-predisposing syndrome	2023-04-11	criteria provided, single submitter	clinical testing	This variant deletes 2 nucleotides in exon 8 of the BRCA2 gene, creating a frameshift and premature translation stop signal. This variant is also known as 886delGT in the literature. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in multiple individuals affected with breast and ovarian cancer (PMID: 9667259, 22923021, 23767878, 24504028, 27153395, 28324225, 28724667, 30287823). It has also been observed in compound heterozygous state with a pathogenic variant in two individuals affected with Fanconi anemia (PMID: 16825431). This variant has been identified in 13/276414 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Loss of BRCA2 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000074548	SCV000296738	pathogenic	not provided	2023-03-02	criteria provided, single submitter	clinical testing	This variant alters the translational reading frame of the BRCA2 mRNA and causes the premature termination of BRCA2 protein synthesis. In the published literature, this variant has been reported in individuals with breast and/or ovarian cancer (PMIDs: 35220195 (2022), 33478551 (2021), 32438681 (2020), 32098980 (2020), 32341426 (2020), 32318955 (2020), 31980526 (2020), 31957001 (2020), 31411802 (2019), 31263054 (2019), 30350268 (2018), 30287823 (2018), 29492181 (2018)). Additionally, the variant has been reported in individuals with prostate cancer (PMIDs: 31948886 (2020), 32875559 (2020)), colorectal cancer (PMID: 26681312 (2015)), mesothelioma (PMID: 34008015 (2021), and esophageal squamous cell carcinoma (PMID: 31396961 (2020)). The variant has occurred with an additional pathogenic BRCA2 variant in children with Fanconi Anemia, Wilm's tumor, and/or medulloblastoma (PMIDs: 29753700 (2018), 26657402 (2016), 26064523 (2015), 16825431 (2007), 15689453 (2005), 14670928 (2004)). The frequency of this variant in the general population, 0.00013 (3/23770 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is consistent with pathogenicity. Based on the available information, this variant is classified as pathogenic.
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge	RCV000031637	SCV000327465	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2015-10-02	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000044988	SCV000494408	pathogenic	Hereditary breast ovarian cancer syndrome	2016-04-18	criteria provided, single submitter	clinical testing	Variant summary: The c.658_659delGT variant results in a premature termination codon, predicted to cause a truncated or absent BRCA2 protein, which is a commonly known mechanism for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (c.755_758delACAG, p.Asp252fsX24; c.771_775delTCAAA, p.Asn257fsX17; c.778_779delGA, p.Glu260fsX15). The variant was observed in the large and broad cohorts of the ExAC project at an allele frequency of 0.006% which does not exceed the maximal expected allele frequency for a pathogenic variant in BRCA2 (0.075%). The variant has been reported in numerous affected individuals in the literature, including 2 siblings affected with Fanconi anemia who also carried a second pathogenic BRCA2 variant (Svojgr_2016). Mutliple reputable clinical labs have classified the variant as "Pathogenic". Taken together, this variant is classified as pathogenic.
Baylor Genetics	RCV000466729	SCV000540998	pathogenic	Familial cancer of breast	2024-02-26	criteria provided, single submitter	clinical testing
HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology	RCV000031637	SCV000584073	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2014-07-10	criteria provided, single submitter	research
Department of Medical Genetics, Oslo University Hospital	RCV000031637	SCV000605688	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2015-10-06	criteria provided, single submitter	clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000044988	SCV000605780	pathogenic	Hereditary breast ovarian cancer syndrome	2022-11-23	criteria provided, single submitter	clinical testing	The p.Val220IlefsX4 variant in BRCA2 has been identified in >50 individuals with BRCA2-associated cancers (Frank 1998 PMID:9667259, Berzina 2013 PMID:23767878, Breast Cancer Information Core (BIC) database: https://research.nhgri.nih.gov/bic/) and in 3 compound heterozygous individuals with Fanconi anemia (Offit 2003 PMID:14559878, Hirsch 2004 PMID:14670928, Reid 2005 PMID:15689453). It has also been identified in 0.012% (5/41438) of African/African American chromosomes and in 0.003% (2/68004) of European chromosomes by gnomAD (http://gnomad.broadinstitute.org, v3.1). This frequency is low enough to be consistent with the frequency of hereditary breast and ovarian cancer (HBOC) in the general population. This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 220 and leads to a premature termination codon 4 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Heterozygous loss of function of the BRCA2 gene is an established disease mechanism in autosomal dominant hereditary breast and ovarian cancer (HBOC). Additionally, this variant was classified as pathogenic on Apr 22, 2016 by the ClinGen-approved ENIGMA expert panel (Variation ID 9342). In summary, this variant meets criteria to be classified as pathogenic for HBOC in an autosomal dominant manner. ACMG/AMP Criteria applied: PS4, PM2_Supporting, PVS1.
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000031637	SCV000744390	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2015-09-21	criteria provided, single submitter	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV000074548	SCV000778635	pathogenic	not provided	2019-10-25	criteria provided, single submitter	clinical testing	PVS1, PM2, PP5
CeGaT Center for Human Genetics Tuebingen	RCV000074548	SCV001247635	pathogenic	not provided	2023-12-01	criteria provided, single submitter	clinical testing	BRCA2: PVS1, PS3:Moderate, PS4:Supporting
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	RCV000074548	SCV001447718	pathogenic	not provided	2020-10-23	criteria provided, single submitter	clinical testing
Clinical Genetics and Genomics, Karolinska University Hospital	RCV000074548	SCV001449833	pathogenic	not provided	2015-11-18	criteria provided, single submitter	clinical testing
Department of Molecular Diagnostics, Institute of Oncology Ljubljana	RCV000210073	SCV001499761	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2020-04-02	criteria provided, single submitter	clinical testing
Institute of Human Genetics, University of Leipzig Medical Center	RCV000031637	SCV001934294	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2023-12-29	criteria provided, single submitter	clinical testing	Criteria applied: PVS1,PM5_STR
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000074548	SCV002049181	pathogenic	not provided	2023-08-10	criteria provided, single submitter	clinical testing	The BRCA2 c.658_659delGT; p.Val220IlefsTer4 variant (rs80359604), also known as 886delGT, is reported in the literature in multiple individuals affected with hereditary breast and ovarian cancer syndrome (Cunningham 2014, de Juan 2015, Frank 1998, Heramb 2018), and in patients with Fanconi anemia when found in-trans with another pathogenic variant (Hirsch 2004, Svojgr 2016). This variant is reported as pathogenic by multiple laboratories in ClinVar (Variation ID: 9342), and is found in the African/African American population with an allele frequency of 0.013% (3/23,770 alleles) in the Genome Aggregation Database. This variant causes a frameshift by deleting 2 nucleotides, so it is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Based on available information, the p.Val220IlefsTer4 variant is considered to be pathogenic. References: Cunningham J et al. Clinical characteristics of ovarian cancer classified by BRCA1, BRCA2, and RAD51C status. Sci Rep. 2014 4:4026. PMID: 24504028. de Juan I et al. BRCA1 and BRCA2 mutations in males with familial breast and ovarian cancer syndrome. Results of a Spanish multicenter study. Fam Cancer. 2015 14(4):505-13. PMID: 26026974. Frank T et al. Sequence analysis of BRCA1 and BRCA2: correlation of mutations with family history and ovarian cancer risk. J Clin Oncol. 1998 16(7):2417-25. PMID: 9667259. Heramb C et al. BRCA1 and BRCA2 mutation spectrum - an update on mutation distribution in a large cancer genetics clinic in Norway. Hered Cancer Clin Pract. 2018 Jan 10;16:3. PMID: 29339979. Hirsch B et al. Association of biallelic BRCA2/FANCD1 mutations with spontaneous chromosomal instability and solid tumors of childhood. Blood. 2004 103(7):2554-9. PMID: 14670928. Svojgr K et al. Fanconi anemia with biallelic FANCD1/BRCA2 mutations - Case report of a family with three affected children. Eur J Med Genet. 2016 59(3):152-7. PMID: 26657402.
Institute of Human Genetics, Clinical Exome/Genome Diagnostics Group, University Hospital Bonn	RCV000466729	SCV002103002	pathogenic	Familial cancer of breast	2021-10-29	criteria provided, single submitter	clinical testing	Incidental finding in clinical exome sequencing. PVS1, PS4, PS5
Institute of Human Genetics, Clinical Exome/Genome Diagnostics Group, University Hospital Bonn	RCV000031637	SCV002103003	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2021-10-29	criteria provided, single submitter	clinical testing	Incidental finding in clinical exome sequencing. PVS1, PS4, PS5
Institute of Human Genetics, Clinical Exome/Genome Diagnostics Group, University Hospital Bonn	RCV001843452	SCV002103004	pathogenic	Malignant tumor of prostate	2021-10-29	criteria provided, single submitter	clinical testing	Incidental finding in clinical exome sequencing. PVS1, PS4, PS5
Institute of Human Genetics, Clinical Exome/Genome Diagnostics Group, University Hospital Bonn	RCV000009932	SCV002103005	pathogenic	Medulloblastoma	2021-10-29	criteria provided, single submitter	clinical testing	Incidental finding in clinical exome sequencing. PVS1, PS4, PS5
Institute of Human Genetics, Clinical Exome/Genome Diagnostics Group, University Hospital Bonn	RCV000009930	SCV002103006	pathogenic	Wilms tumor 1	2021-10-29	criteria provided, single submitter	clinical testing	Incidental finding in clinical exome sequencing. PVS1, PS4, PS5
Sema4, Sema4	RCV000131858	SCV002536247	pathogenic	Hereditary cancer-predisposing syndrome	2021-02-10	criteria provided, single submitter	curation
Fulgent Genetics, Fulgent Genetics	RCV002496316	SCV002812445	pathogenic	Familial cancer of breast; Breast-ovarian cancer, familial, susceptibility to, 2; Fanconi anemia complementation group D1; Medulloblastoma; Wilms tumor 1; Malignant tumor of prostate; Pancreatic cancer, susceptibility to, 2; Glioma susceptibility 3	2021-10-29	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000074548	SCV003802786	pathogenic	not provided	2022-09-19	criteria provided, single submitter	clinical testing	The BRCA2 c.658_659delGT (p.Val220IlefsTer4) variant results in the deletion of two nucleotides at position c.658-659, causing a shift in the protein reading frame that is predicted to result in premature termination of the protein. Loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay is expected. Across a selection of the available literature, the c.658_659delGT variant, also referred to as c.886delGT, has been identified in a heterozygous state in at least eight individuals with breast cancer and one individual with ovarian cancer (PMID: 9667259; PMID: 23767878; PMID: 24504028; PMID: 27153395). The variant has also been observed in a compound heterozygous state in at least seven individuals with Fanconi anemia (PMID: 14670928; PMID: 26064523). The highest frequency of this allele in the Genome Aggregation Database is 0.000126 in the African/African-American population. Based on the available evidence the c.658_659delGT (p.Val220IlefsTer4) variant is classified as pathogenic for hereditary breast and ovarian cancer.
Revvity Omics, Revvity	RCV000074548	SCV003814404	pathogenic	not provided	2023-03-03	criteria provided, single submitter	clinical testing
Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego	RCV003335024	SCV004046239	pathogenic	BRCA2-related disorder		criteria provided, single submitter	clinical testing	This frameshifting variant in exon 8 of 28 introduces a premature stop codon and is therefore predicted to result in loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay (NMD). This variant has been previously reported in individuals with breast and ovarian cancer (PMID: 22923021, 23767878, 28324225). This variant has also been reported as a compound heterozygous change in patients with Fanconi anemia (PMID: 16825431). Loss-of-function variation in BRCA2 is an established mechanism of disease (PMID: 20104584). The c.658_659del (p.Val220IlefsTer4) variant is present in the heterozygous state in the gnomAD population database at a frequency of 0.005% (13/276414) and thus is presumed to be rare. Based on the available evidence, the c.658_659del (p.Val220IlefsTer4) variant is classified as Pathogenic.
All of Us Research Program, National Institutes of Health	RCV000031637	SCV004846802	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2024-01-08	criteria provided, single submitter	clinical testing	The c.658_659delGT (p.Val220Ilefs*4) variant in the BRCA2 gene is located on the exon 8 and is predicted to cause reading frame shift that introduces a premature translation termination codon (p.Val220Ilefs*4), resulting in an absent or disrupted protein product. Loss-of-function variants of BRCA2 are known to be pathogenic (PMID: 11897832). This c.658_659delGT variant was reported in more than 10 unrelated individuals with ovarian/breast cancer (PMID: 33478551, 34097676, 33670479, 32571290, 32824581, 22923021). It is one of the most frequently observed BRCA2 variants in North America and Lithuania, and more than 20 families were reported with the variant and disease (PMID: 29446198). This variant is reported in ClinVar as pathogenic (ID: 9342) and reviewed by the expert panel. The variant is rare in the general population according to gnomAD (13/276414). Therefore, the c.658_659delGT (p.Val220Ilefs*4) variant of BRCA2 has been classified as pathogenic.
Cancer Genomics Group, Japanese Foundation For Cancer Research	RCV000044988	SCV005045658	likely pathogenic	Hereditary breast ovarian cancer syndrome	2023-03-27	criteria provided, single submitter	research
Clinical Genetics Laboratory, Skane University Hospital Lund	RCV000074548	SCV005196833	pathogenic	not provided	2022-05-27	criteria provided, single submitter	clinical testing
OMIM	RCV000009929	SCV000030150	pathogenic	Fanconi anemia complementation group D1	2007-01-01	no assertion criteria provided	literature only
OMIM	RCV000009930	SCV000030151	pathogenic	Wilms tumor 1	2007-01-01	no assertion criteria provided	literature only
OMIM	RCV000009931	SCV000030152	risk factor	Glioma susceptibility 3	2007-01-01	no assertion criteria provided	literature only
OMIM	RCV000009932	SCV000030153	pathogenic	Medulloblastoma	2007-01-01	no assertion criteria provided	literature only
Sharing Clinical Reports Project (SCRP)	RCV000031637	SCV000054244	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2014-01-04	no assertion criteria provided	clinical testing
Breast Cancer Information Core (BIC) (BRCA2)	RCV000031637	SCV000147427	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2002-05-29	no assertion criteria provided	clinical testing
Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto	RCV000044988	SCV000587560	pathogenic	Hereditary breast ovarian cancer syndrome	2014-01-31	no assertion criteria provided	research
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000031637	SCV000733216	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2		no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003335024	SCV000805748	pathogenic	BRCA2-related disorder	2024-06-25	no assertion criteria provided	clinical testing	The BRCA2 c.658_659delGT variant is predicted to result in a frameshift and premature protein termination (p.Val220Ilefs*4). This variant is alternatively described as c.658delGT, c.886delGT or c.886_887delGT. This variant has been observed in individuals with personal and family histories of breast and/or ovarian cancer (Novakovic et al. 2012. PubMed ID: 22923021; Berzina et al. 2013. PubMed ID: 23767878; Tung et al. 2016. PubMed ID: 26976419), Fanconi anemia (group D1), and other types of malignancies, including brain tumors (Offit et al. 2003. PubMed ID: 14559878; Reid et al. 2005. PubMed ID: 15689453; Alter et al. 2006, PubMed ID: 16825431). This variant, in combination with another variant in the same or a different gene, has also been reported in individuals with multiple malignancies including colorectal cancer (Heidemann et al. 2012. PubMed ID: 22535016; Degrolard-Courcet et al. 2014, PubMed ID: 24301060). This variant is reported in 0.013% of alleles in individuals of African descent in gnomAD. In ClinVar, it has been classified as pathogenic (https://www.ncbi.nlm.nih.gov/clinvar/variation/9342). Frameshift variants in BRCA2 are expected to be pathogenic. This variant is interpreted as pathogenic.
Foulkes Cancer Genetics LDI, Lady Davis Institute for Medical Research	RCV000735587	SCV000863725	pathogenic	Breast and/or ovarian cancer	2016-12-04	no assertion criteria provided	clinical testing
CZECANCA consortium	RCV000735587	SCV001451877	pathogenic	Breast and/or ovarian cancer	2019-06-11	no assertion criteria provided	case-control
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001356991	SCV001552307	pathogenic	Malignant tumor of breast		no assertion criteria provided	clinical testing	The BRCA2 p.Val220Ilefs*4 variant was identified in 19 of 19400 proband chromosomes (frequency: 0.001) from individuals or families with breast or ovarian cancer (Bayraktar 2012, Berzina 2013, Frank 1998, Heidemann 2012, Janavicius 2014, Novakovic 2012). The variant was also identified in the case study in two siblings with Fanconi anemia with biallelic FANCD1/BRCA2 mutations (Svojgr 2016). The variant was also identified in dbSNP (ID: rs80359604) as “With Pathogenic allele”, ClinVar (classified as pathogenic by Invitae, Ambry Genetics, GeneDx and seventeen other submitters), LOVD 3.0 (58X as pathogenic), and in UMD-LSDB (30X as causal). This mutation was found at a high frequency in the Lithuanian population and could represent a Baltic founder mutation (Janavicius 2014).The variant was not identified in the following control databases: the Exome Aggregation Consortium (August 8th 2016), or the Genome Aggregation Database (Feb 27, 2017). The c.658_659del variant is predicted to cause a frameshift, which alters the protein's amino acid sequence beginning at codon 220 and leads to a premature stop codon at position 223. This alteration is then predicted to result in a truncated or absent protein and loss of function. Loss of function variants of the BRCA2 gene are an established mechanism of disease in BRCA associated cancers and is the type of variant expected to cause the disorder. In summary, based on the above information this variant meets our laboratory’s criteria to be classified as pathogenic.
Center for Precision Medicine, Meizhou People's Hospital	RCV000466729	SCV002520927	pathogenic	Familial cancer of breast		no assertion criteria provided	literature only
BRCAlab, Lund University	RCV000031637	SCV002588849	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2022-08-26	no assertion criteria provided	clinical testing
Laboratory for Genotyping Development, RIKEN	RCV003162226	SCV002758326	pathogenic	Gastric cancer	2021-07-01	no assertion criteria provided	research
CZECANCA consortium	RCV003128126	SCV003804356	pathogenic	Uterine corpus cancer	2023-02-21	no assertion criteria provided	clinical testing