Submissions for variant NM_000059.4(BRCA2):c.10220A>G (p.Asn3407Ser)

dbSNP: rs80358401

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000129602	SCV000184387	likely benign	Hereditary cancer-predisposing syndrome	2019-01-29	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.
GeneDx	RCV000589028	SCV000210700	likely benign	not provided	2018-09-11	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 24817641)
Counsyl	RCV000112850	SCV000488149	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 2	2016-03-03	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000212294	SCV000694500	uncertain significance	not specified	2021-04-06	criteria provided, single submitter	clinical testing	Variant summary: BRCA2 c.10220A>G (p.Asn3407Ser) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 250846 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.10220A>G in individuals affected with Hereditary Breast And Ovarian Cancer Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation (likely benign, n=3; VUS, n=2). Based on the evidence outlined above, the variant was classified as uncertain significance.
Color Diagnostics, LLC DBA Color Health	RCV000129602	SCV000906968	likely benign	Hereditary cancer-predisposing syndrome	2018-08-30	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001370256	SCV001566726	likely benign	Hereditary breast ovarian cancer syndrome	2024-10-30	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV000589028	SCV003830145	uncertain significance	not provided	2022-06-27	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV000112850	SCV004846281	likely benign	Breast-ovarian cancer, familial, susceptibility to, 2	2023-12-13	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000589028	SCV005624312	uncertain significance	not provided	2024-11-12	criteria provided, single submitter	clinical testing	The BRCA2 c.10220A>G (p.Asn3407Ser) has been observed in a large scale breast cancer association study in a reportedly healthy individual (PMID: 33471991 (2021), see also LOVD (http://databases.lovd.nl/shared)). The frequency of this variant in the general population, 0.000004 (1/250846 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant.
Breast Cancer Information Core (BIC) (BRCA2)	RCV000112850	SCV000145767	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 2		no assertion criteria provided	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV000589028	SCV000592317	uncertain significance	not provided		no assertion criteria provided	clinical testing