Submissions for variant NM_000059.4(BRCA2):c.2103_2106del (p.Phe701fs)

dbSNP: rs80359324

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000113014	SCV000300493	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	RCV000214908	SCV000273000	pathogenic	Hereditary cancer-predisposing syndrome	2022-02-04	criteria provided, single submitter	clinical testing	The c.2103_2106delTATT pathogenic mutation, located in coding exon 10 of the BRCA2 gene, results from a deletion of 4 nucleotides at nucleotide positions 2103 to 2106, causing a translational frameshift with a predicted alternate stop codon (p.F701Lfs*28). This alteration has previously been reported in an Italian female diagnosed with breast cancer (Nedelcu R et al. Eur. J. Hum. Genet. 2002 Feb;10(2):150-2). This alteration was also identified in a large, worldwide study of BRCA1/2 mutation positive families (Rebbeck TR et al. Hum Mutat, 2018 05;39:593-620). Of note, this alteration is also designated as 2331delTATT in published literature. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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.
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge	RCV000113014	SCV000326656	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2015-10-02	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000508584	SCV000602856	pathogenic	not specified	2017-01-13	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000496930	SCV000694590	pathogenic	Hereditary breast ovarian cancer syndrome	2016-04-25	criteria provided, single submitter	clinical testing	Variant summary: The c.2103_2106delTATT variant is predicted to cause a frameshift, which alters the proteins amino acid sequence beginning at position 701 and leads to a premature termination codon 27 amino acids downstream. It is 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 (e.g. c.2564_2565delCA/p.T855fs). Mutation taster predicts damaging outcome for this variant. This variant is not found in 120680 control chromosomes. This variant has been reported in an Italian BrC family (Nedelcu_BRCA1&2_EJHG_2002). In addition, multiple reputable databases (BIC, ARUP) classified this variant as pathogenic. Taken together, this variant was classified as a Pathogenic.
Color Diagnostics, LLC DBA Color Health	RCV000214908	SCV001358927	pathogenic	Hereditary cancer-predisposing syndrome	2020-01-15	criteria provided, single submitter	clinical testing	This variant deletes 4 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 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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000496930	SCV001401070	pathogenic	Hereditary breast ovarian cancer syndrome	2023-07-10	criteria provided, single submitter	clinical testing	This variant is also known as c.2331delTATT. ClinVar contains an entry for this variant (Variation ID: 51244). For these reasons, this variant has been classified as Pathogenic. This premature translational stop signal has been observed in individual(s) with breast and/or ovarian cancer (PMID: 11938448). This sequence change creates a premature translational stop signal (p.Phe701Leufs*28) 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).
Baylor Genetics	RCV003473310	SCV004210500	pathogenic	Familial cancer of breast	2022-09-02	criteria provided, single submitter	clinical testing
Breast Cancer Information Core (BIC) (BRCA2)	RCV000113014	SCV000146005	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	1999-06-21	no assertion criteria provided	clinical testing
Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto	RCV000496930	SCV000587623	pathogenic	Hereditary breast ovarian cancer syndrome	2014-01-31	no assertion criteria provided	research
BRCAlab, Lund University	RCV000113014	SCV004244242	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2020-03-02	no assertion criteria provided	clinical testing