ClinVar Miner

Submissions for variant NM_000057.4(BLM):c.1612G>C (p.Ala538Pro)

gnomAD frequency: 0.00001  dbSNP: rs1318049766
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000799272 SCV000938927 uncertain significance Bloom syndrome 2022-10-13 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 538 of the BLM protein (p.Ala538Pro). This variant is present in population databases (no rsID available, gnomAD no frequency). This variant has not been reported in the literature in individuals affected with BLM-related conditions. ClinVar contains an entry for this variant (Variation ID: 645228). 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 BLM 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.
Ambry Genetics RCV002397601 SCV002707942 uncertain significance Hereditary cancer-predisposing syndrome 2022-07-07 criteria provided, single submitter clinical testing The p.A538P variant (also known as c.1612G>C), located in coding exon 6 of the BLM gene, results from a G to C substitution at nucleotide position 1612. The alanine at codon 538 is replaced by proline, an amino acid with highly 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.
GeneDx RCV003235399 SCV003933189 uncertain significance not provided 2022-12-19 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Natera, Inc. RCV000799272 SCV002092376 uncertain significance Bloom syndrome 2018-09-02 no assertion criteria provided clinical testing

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