Submissions for variant NM_000059.4(BRCA2):c.2657A>T (p.Asn886Ile)

dbSNP: rs80358526

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001345499	SCV001539622	uncertain significance	Hereditary breast ovarian cancer syndrome	2023-08-14	criteria provided, single submitter	clinical testing	In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt BRCA2 protein function. ClinVar contains an entry for this variant (Variation ID: 51323). This missense change has been observed in individual(s) with clinical features of BRCA2-related conditions (PMID: 10923033, 21520333). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces asparagine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 886 of the BRCA2 protein (p.Asn886Ile).
GeneDx	RCV003153334	SCV003842904	uncertain significance	not provided	2022-09-19	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; Also known as 2885A>T; This variant is associated with the following publications: (PMID: 31871109)
University of Washington Department of Laboratory Medicine, University of Washington	RCV003156751	SCV003848479	likely benign	Hereditary cancer-predisposing syndrome	2023-03-23	criteria provided, single submitter	curation	Missense variant in a coldspot region where missense variants are very unlikely to be pathogenic (PMID:31911673).
Ambry Genetics	RCV003156751	SCV005548600	likely benign	Hereditary cancer-predisposing syndrome	2024-07-01	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.
Breast Cancer Information Core (BIC) (BRCA2)	RCV000113074	SCV000146085	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 2	1998-11-30	no assertion criteria provided	clinical testing
BRCAlab, Lund University	RCV000113074	SCV004244248	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 2	2020-03-02	no assertion criteria provided	clinical testing