ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.8201C>T (p.Pro2734Leu)

gnomAD frequency: 0.00001  dbSNP: rs876658732
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000223518 SCV000274382 uncertain significance Hereditary cancer-predisposing syndrome 2023-05-16 criteria provided, single submitter clinical testing The p.P2734L variant (also known as c.8201C>T), located in coding exon 17 of the BRCA2 gene, results from a C to T substitution at nucleotide position 8201. The proline at codon 2734 is replaced by leucine, an amino acid with similar properties. This alteration has been detected in 1/2575 unselected patients with breast cancer and 0/2809 healthy control individuals from a Malaysian cohort (Wen WX et al. J Med Genet. 2018 02;55:97-103). 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV000558611 SCV000635646 uncertain significance Hereditary breast ovarian cancer syndrome 2022-01-04 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: 230730). This missense change has been observed in individual(s) with breast cancer (PMID: 28993434). This variant is present in population databases (no rsID available, gnomAD 0.007%). This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 2734 of the BRCA2 protein (p.Pro2734Leu).
PreventionGenetics, part of Exact Sciences RCV004532781 SCV004114200 uncertain significance BRCA2-related disorder 2022-10-04 criteria provided, single submitter clinical testing The BRCA2 c.8201C>T variant is predicted to result in the amino acid substitution p.Pro2734Leu. This variant has been reported as a variant of uncertain significance in a cohort of individuals with breast cancer (Table S5 in Wen et al. 2018. PubMed ID: 28993434). This variant is reported in 0.0062% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/13-32937540-C-T), and is classified in ClinVar as uncertain (https://www.ncbi.nlm.nih.gov/clinvar/variation/230730). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Baylor Genetics RCV004567528 SCV005059019 uncertain significance Familial cancer of breast 2024-03-01 criteria provided, single submitter clinical testing

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