Submissions for variant NM_000059.4(BRCA2):c.9958C>T (p.Pro3320Ser)

dbSNP: rs1300220263

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000508391	SCV000600885	uncertain significance	not specified	2017-03-10	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000565180	SCV000668785	uncertain significance	Hereditary cancer-predisposing syndrome	2024-01-31	criteria provided, single submitter	clinical testing	The p.P3320S variant (also known as c.9958C>T), located in coding exon 26 of the BRCA2 gene, results from a C to T substitution at nucleotide position 9958. The proline at codon 3320 is replaced by serine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Color Diagnostics, LLC DBA Color Health	RCV000565180	SCV000912355	uncertain significance	Hereditary cancer-predisposing syndrome	2019-04-24	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001210237	SCV001381712	uncertain significance	Hereditary breast ovarian cancer syndrome	2024-09-01	criteria provided, single submitter	clinical testing	This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 3320 of the BRCA2 protein (p.Pro3320Ser). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with BRCA2-related conditions. ClinVar contains an entry for this variant (Variation ID: 439024). 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000508391	SCV005040207	uncertain significance	not specified	2024-03-05	criteria provided, single submitter	clinical testing	Variant summary: BRCA2 c.9958C>T (p.Pro3320Ser) results in a non-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 was absent in 251146 control chromosomes (gnomAD). 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.9958C>T in individuals affected with Hereditary Breast And Ovarian Cancer Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 439024). Based on the evidence outlined above, the variant was classified as uncertain significance.
All of Us Research Program, National Institutes of Health	RCV004806380	SCV005425870	uncertain significance	BRCA2-related cancer predisposition	2024-02-22	criteria provided, single submitter	clinical testing	This missense variant replaces proline with serine at codon 3320 of the BRCA2 protein. Computational prediction suggests that this variant may not impact protein structure and function. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with BRCA2-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.