Submissions for variant NM_000059.4(BRCA2):c.6959T>C (p.Leu2320Ser)

dbSNP: rs80358923

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000509856	SCV000607795	uncertain significance	Hereditary cancer-predisposing syndrome	2022-08-04	criteria provided, single submitter	clinical testing	The p.L2320S variant (also known as c.6959T>C), located in coding exon 12 of the BRCA2 gene, results from a T to C substitution at nucleotide position 6959. The leucine at codon 2320 is replaced by serine, an amino acid with dissimilar properties. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Color Diagnostics, LLC DBA Color Health	RCV000509856	SCV000683833	uncertain significance	Hereditary cancer-predisposing syndrome	2019-06-11	criteria provided, single submitter	clinical testing
Counsyl	RCV000113679	SCV000785034	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 2	2017-03-22	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001251343	SCV001426907	uncertain significance	not specified	2020-07-13	criteria provided, single submitter	clinical testing	Variant summary: BRCA2 c.6959T>C (p.Leu2320Ser) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 249948 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.6959T>C in individuals affected with Hereditary Breast And Ovarian Cancer Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001341874	SCV001535770	uncertain significance	Hereditary breast ovarian cancer syndrome	2024-11-12	criteria provided, single submitter	clinical testing	This sequence change replaces leucine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 2320 of the BRCA2 protein (p.Leu2320Ser). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of BRCA2-related conditions (PMID: 21520333). ClinVar contains an entry for this variant (Variation ID: 52227). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt BRCA2 protein function with a negative predictive value of 95%. 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.
All of Us Research Program, National Institutes of Health	RCV004803885	SCV005424563	uncertain significance	BRCA2-related cancer predisposition	2024-03-05	criteria provided, single submitter	clinical testing
Breast Cancer Information Core (BIC) (BRCA2)	RCV000113679	SCV000146982	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 2	2004-02-20	no assertion criteria provided	clinical testing