ClinVar Miner

Submissions for variant NM_000057.4(BLM):c.2843C>A (p.Ala948Glu)

dbSNP: rs1156545383
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000803695 SCV000943578 uncertain significance Bloom syndrome 2024-03-10 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 948 of the BLM protein (p.Ala948Glu). This variant is not present in population databases (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: 648879). 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 expected to disrupt BLM protein function with a positive predictive value of 80%. 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 RCV002440698 SCV002746548 uncertain significance Hereditary cancer-predisposing syndrome 2024-07-22 criteria provided, single submitter clinical testing The p.A948E variant (also known as c.2843C>A), located in coding exon 14 of the BLM gene, results from a C to A substitution at nucleotide position 2843. The alanine at codon 948 is replaced by glutamic acid, an amino acid with dissimilar properties. This alteration was identified in an individual diagnosed with colorectal cancer (DeRycke MS et al. Mol Genet Genomic Med, 2017 Sep;5:553-569). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear.

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