Submissions for variant NM_000059.4(BRCA2):c.3009_3010del (p.His1003fs)

dbSNP: rs397507300

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000031395	SCV000300580	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2016-09-08	reviewed by expert panel	curation	Variant allele predicted to encode a truncated non-functional protein.
Ambry Genetics	RCV000132309	SCV000187395	pathogenic	Hereditary cancer-predisposing syndrome	2023-02-16	criteria provided, single submitter	clinical testing	The c.3009_3010delCA pathogenic mutation, located in coding exon 10 of the BRCA2 gene, results from a deletion of two nucleotides at nucleotide positions 3009 to 3010, causing a translational frameshift with a predicted alternate stop codon (p.H1003Qfs*5). This alteration was identified in multiple individuals with HBOC related cancers (Sharma et al. Acta Oncol 2016 May;55(3):377-81; Rebbeck et al. Hum. Mutat. 2018 05;39(5):593-620). This mutation was also described in the literature as c.3237_3238delCA. 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 interpreted as a disease-causing mutation.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000232051	SCV000283199	pathogenic	Hereditary breast ovarian cancer syndrome	2023-07-13	criteria provided, single submitter	clinical testing	ClinVar contains an entry for this variant (Variation ID: 37814). This sequence change creates a premature translational stop signal (p.His1003Glnfs*5) 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 not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with clinical features of BRCA2-related conditions (PMID: 21520333). For these reasons, this variant has been classified as Pathogenic.
GeneDx	RCV000255011	SCV000321455	pathogenic	not provided	2021-11-04	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 individuals with a personal or family history of BRCA2-related cancers (Sharma et al., 2016; Palmer et al., 2020); Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); Also known as 3237_3238del; This variant is associated with the following publications: (PMID: 28152038, 32427313, 26004055)
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge	RCV000031395	SCV000326800	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2015-10-02	criteria provided, single submitter	clinical testing
Counsyl	RCV000031395	SCV000677710	likely pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2017-01-25	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV000255011	SCV002022579	pathogenic	not provided	2019-08-14	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000132309	SCV004361990	pathogenic	Hereditary cancer-predisposing syndrome	2023-01-03	criteria provided, single submitter	clinical testing	This variant deletes 2 nucleotides in exon 11 of the BRCA2 gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been detected in an individual affected with pancreatic cancer (PMID: 26004055). This variant has not been identified 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.
All of Us Research Program, National Institutes of Health	RCV000031395	SCV004845096	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2023-05-16	criteria provided, single submitter	clinical testing	This variant deletes 2 nucleotides in exon 11 of the BRCA2 gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been detected in an individual affected with pancreatic cancer (PMID: 26004055). This variant has not been identified 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.
Baylor Genetics	RCV004566768	SCV005059071	pathogenic	Familial cancer of breast	2024-02-06	criteria provided, single submitter	clinical testing
Juno Genomics, Hangzhou Juno Genomics, Inc	RCV004795940	SCV005416546	pathogenic	Familial cancer of breast; Breast-ovarian cancer, familial, susceptibility to, 2		criteria provided, single submitter	clinical testing	PM2_Supporting+PVS1+PS4_Supporting
Sharing Clinical Reports Project (SCRP)	RCV000031395	SCV000054000	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2011-08-09	no assertion criteria provided	clinical testing