ClinVar Miner

Submissions for variant NM_000057.4(BLM):c.2212A>G (p.Thr738Ala)

dbSNP: rs1050741211
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000800717 SCV000940447 uncertain significance Bloom syndrome 2018-07-26 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with BLM-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces threonine with alanine at codon 738 of the BLM protein (p.Thr738Ala). The threonine residue is moderately conserved and there is a small physicochemical difference between threonine and alanine.
Ambry Genetics RCV003344057 SCV004051465 uncertain significance Hereditary cancer-predisposing syndrome 2023-06-27 criteria provided, single submitter clinical testing The p.T738A variant (also known as c.2212A>G), located in coding exon 9 of the BLM gene, results from an A to G substitution at nucleotide position 2212. The threonine at codon 738 is replaced by alanine, an amino acid with similar properties. This amino acid position is 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.
St. Jude Molecular Pathology, St. Jude Children's Research Hospital RCV000800717 SCV005402386 uncertain significance Bloom syndrome 2024-01-08 criteria provided, single submitter clinical testing The BLM c.2212A>G (p.Thr738Ala) missense change is absent in gnomAD v2.1.1 (https://gnomad.broadinstitute.org). The in silico tool REVEL predicts a benign effect on protein function, but to our knowledge this prediction has not been confirmed by functional studies. To our knowledge, this variant has not been reported in individuals with Bloom syndrome. In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance.
Natera, Inc. RCV000800717 SCV002088046 uncertain significance Bloom syndrome 2020-01-16 no assertion criteria provided clinical testing

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