ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.3449C>G (p.Thr1150Ser)

dbSNP: rs730881524
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000160064 SCV000210316 uncertain significance not provided 2014-09-09 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.3449C>G at the cDNA level, p.Thr1150Ser (T1150S) at the protein level, and results in the change of a Threonine to a Serine (ACT>AGT). This variant also referred to as c.3677C>G has not, to our knowledge, been published in the literature as pathogenic or benign. BRCA2 Thr1150Ser was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Since Threonine and Serine share similar properties, this is considered a conservative amino acid substitution. BRCA2 Thr1150Ser occurs at a position that is poorly conserved across species while tolerating Serine in four species and is not located within a known functional domain. In silico analyses predict that this variant is unlikely to alter protein structure or function. Based on currently available information, it is unclear whether BRCA2 Thr1150Ser is pathogenic or benign. We consider it to be a variant of uncertain significance.
Ambry Genetics RCV002453560 SCV002616187 uncertain significance Hereditary cancer-predisposing syndrome 2020-09-09 criteria provided, single submitter clinical testing The p.T1150S variant (also known as c.3449C>G), located in coding exon 10 of the BRCA2 gene, results from a C to G substitution at nucleotide position 3449. The threonine at codon 1150 is replaced by serine, an amino acid with similar properties. This amino acid position is poorly 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.
University of Washington Department of Laboratory Medicine, University of Washington RCV002453560 SCV003851973 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).

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