Submissions for variant NM_000059.4(BRCA2):c.162CAA[1] (p.Asn56del)

dbSNP: rs11571587

Total submissions: 15

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV001091525	SCV000210657	likely benign	not provided	2021-09-22	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 29988080)
Ambry Genetics	RCV000164468	SCV000215112	likely benign	Hereditary cancer-predisposing syndrome	2018-07-16	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000205603	SCV000261016	likely benign	Hereditary breast ovarian cancer syndrome	2024-01-07	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000164468	SCV000683436	benign	Hereditary cancer-predisposing syndrome	2016-12-01	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000160245	SCV000916838	likely benign	not specified	2024-03-14	criteria provided, single submitter	clinical testing	Variant summary: BRCA2 c.165_167delCAA (p.Asn56del) results in an in-frame deletion that is predicted to remove one amino acid from the encoded protein. The variant allele was found at a frequency of 2e-05 in 251382 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance.c.165_167delCAA variant has been reported in several affected individuals via publications without strong evidence for causality (example: de Juan Jimenez_2011). This report does not provide unequivocal conclusions about association of the variant with Hereditary Breast And Ovarian Cancer Syndrome. Co-occurrences with other pathogenic variants have been reported (BIC) and observed internally (BRCA2 c.1929_1929delG, p.Arg645fs; BRCA1 c.5177_5180delGAAA, p.Arg1726fs; BRCA2 c.3744_3747delTGAG, p.Ser1248fs), providing supporting evidence for a benign role. At least one publication reports experimental evidence evaluating an impact on protein function. These results showed variant was complementation positive with a 70% HDR capacity and an 84% cisplatin sensitivity (Mesman_2018). The following publications have been ascertained in the context of this evaluation (PMID: 19941162, 20167696, 21147080, 29988080). ClinVar contains an entry for this variant (Variation ID: 96767). Based on the evidence outlined above, the variant was classified as likely benign.
CeGaT Center for Human Genetics Tuebingen	RCV001091525	SCV001247633	likely benign	not provided	2023-11-01	criteria provided, single submitter	clinical testing	BRCA2: PM4:Supporting, BP4, BS3:Supporting
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV001091525	SCV002047315	likely benign	not provided	2023-05-15	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000160245	SCV002069158	likely benign	not specified	2018-04-24	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000164468	SCV002533249	likely benign	Hereditary cancer-predisposing syndrome	2021-06-23	criteria provided, single submitter	curation
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000160245	SCV004027390	likely benign	not specified	2023-08-15	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV003492433	SCV004240293	uncertain significance	Breast and/or ovarian cancer	2022-07-29	criteria provided, single submitter	clinical testing
Sharing Clinical Reports Project (SCRP)	RCV000082888	SCV000114962	benign	Breast-ovarian cancer, familial, susceptibility to, 2	2010-01-28	no assertion criteria provided	clinical testing
Breast Cancer Information Core (BIC) (BRCA2)	RCV000082888	SCV000146283	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 2	2004-02-20	no assertion criteria provided	clinical testing
BRCAlab, Lund University	RCV000082888	SCV004243648	likely benign	Breast-ovarian cancer, familial, susceptibility to, 2	2020-03-02	no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004542799	SCV004757482	likely benign	BRCA2-related disorder	2022-11-03	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).