ClinVar Miner

Submissions for variant NM_000057.4(BLM):c.4177A>G (p.Asn1393Asp)

gnomAD frequency: 0.00001  dbSNP: rs548600410
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000815041 SCV000955482 uncertain significance Bloom syndrome 2024-12-09 criteria provided, single submitter clinical testing This sequence change replaces asparagine, which is neutral and polar, with aspartic acid, which is acidic and polar, at codon 1393 of the BLM protein (p.Asn1393Asp). This variant is present in population databases (rs548600410, gnomAD 0.002%). 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: 658251). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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 RCV001021993 SCV001183679 uncertain significance Hereditary cancer-predisposing syndrome 2024-04-24 criteria provided, single submitter clinical testing The p.N1393D variant (also known as c.4177A>G), located in coding exon 21 of the BLM gene, results from an A to G substitution at nucleotide position 4177. The asparagine at codon 1393 is replaced by aspartic acid, an amino acid with highly similar 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 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.
Sema4, Sema4 RCV001021993 SCV002533084 uncertain significance Hereditary cancer-predisposing syndrome 2021-10-27 criteria provided, single submitter curation
Fulgent Genetics, Fulgent Genetics RCV000815041 SCV002791459 uncertain significance Bloom syndrome 2024-05-30 criteria provided, single submitter clinical testing
GeneDx RCV003324800 SCV004030552 uncertain significance not provided 2023-02-27 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; This variant is associated with the following publications: (PMID: 28944238)
Quest Diagnostics Nichols Institute San Juan Capistrano RCV003324800 SCV005624282 uncertain significance not provided 2024-10-11 criteria provided, single submitter clinical testing The BLM c.4177A>G (p.Asn1393Asp) variant has been reported in the published literature in an individual with colorectal cancer (PMID: 28944238 (2017)). The frequency of this variant in the general population, 0.000008 (2/251472 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant.
Natera, Inc. RCV000815041 SCV001461030 uncertain significance Bloom syndrome 2020-09-16 no assertion criteria provided clinical testing

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