ClinVar Miner

Submissions for variant NM_000057.4(BLM):c.2662T>C (p.Tyr888His)

gnomAD frequency: 0.00001  dbSNP: rs758696992
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000560159 SCV000623282 uncertain significance Bloom syndrome 2023-06-27 criteria provided, single submitter clinical testing ClinVar contains an entry for this variant (Variation ID: 454112). 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 output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The histidine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. This variant has not been reported in the literature in individuals affected with BLM-related conditions. This variant is present in population databases (rs758696992, gnomAD 0.0009%). This sequence change replaces tyrosine, which is neutral and polar, with histidine, which is basic and polar, at codon 888 of the BLM protein (p.Tyr888His).
Sema4, Sema4 RCV002257782 SCV002529448 uncertain significance Hereditary cancer-predisposing syndrome 2022-02-07 criteria provided, single submitter curation
Ambry Genetics RCV002257782 SCV002739490 likely benign Hereditary cancer-predisposing syndrome 2021-10-15 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV003478098 SCV004222460 uncertain significance not provided 2023-02-09 criteria provided, single submitter clinical testing To the best of our knowledge, the variant has not been reported in the published literature. The frequency of this variant in the general population, 0.000004 (1/250992 chromosomes, http://gnomad.broadinstitute.org), is uninformative in 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. RCV000560159 SCV002088099 uncertain significance Bloom syndrome 2021-05-26 no assertion criteria provided clinical testing

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