ClinVar Miner

Submissions for variant NM_000057.4(BLM):c.2619G>C (p.Lys873Asn)

gnomAD frequency: 0.00006  dbSNP: rs146723808
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000469889 SCV000543360 uncertain significance Bloom syndrome 2022-11-01 criteria provided, single submitter clinical testing This sequence change replaces lysine, which is basic and polar, with asparagine, which is neutral and polar, at codon 873 of the BLM protein (p.Lys873Asn). This variant is present in population databases (rs146723808, gnomAD 0.01%). 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: 405297). 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. Experimental studies have shown that this missense change does not substantially affect BLM function (PMID: 23129629). 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 RCV000570597 SCV000672945 likely benign Hereditary cancer-predisposing syndrome 2020-01-17 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: 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.
Fulgent Genetics, Fulgent Genetics RCV000469889 SCV000896486 uncertain significance Bloom syndrome 2018-10-31 criteria provided, single submitter clinical testing
GeneDx RCV003105908 SCV003761717 uncertain significance not provided 2022-12-08 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; Published functional studies demonstrate DNA damage response comparable to wild type (Mirzaei et al., 2012); This variant is associated with the following publications: (PMID: 23129629)
Natera, Inc. RCV000469889 SCV001454860 uncertain significance Bloom syndrome 2020-09-16 no assertion criteria provided clinical testing

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