ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.9349C>T (p.His3117Tyr)

dbSNP: rs2073022451
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV001176712 SCV001340755 uncertain significance Hereditary cancer-predisposing syndrome 2019-10-09 criteria provided, single submitter clinical testing This missense variant replaces histidine with tyrosine at codon 3117 of the BRCA2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with hereditary cancer 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.
Ambry Genetics RCV001176712 SCV003855521 uncertain significance Hereditary cancer-predisposing syndrome 2022-12-05 criteria provided, single submitter clinical testing The p.H3117Y variant (also known as c.9349C>T), located in coding exon 24 of the BRCA2 gene, results from a C to T substitution at nucleotide position 9349. The histidine at codon 3117 is replaced by tyrosine, an amino acid with similar 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.
Baylor Genetics RCV003462646 SCV004216160 uncertain significance Familial cancer of breast 2023-05-05 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV003530177 SCV004272984 uncertain significance Hereditary breast ovarian cancer syndrome 2023-06-17 criteria provided, single submitter clinical testing 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. 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. ClinVar contains an entry for this variant (Variation ID: 918876). This sequence change replaces histidine, which is basic and polar, with tyrosine, which is neutral and polar, at codon 3117 of the BRCA2 protein (p.His3117Tyr). 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.
All of Us Research Program, National Institutes of Health RCV004006318 SCV004846158 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 2 2023-11-30 criteria provided, single submitter clinical testing This missense variant replaces histidine with tyrosine at codon 3117 of the BRCA2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with hereditary cancer 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.

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