ClinVar Miner

Submissions for variant NM_004260.4(RECQL4):c.2492A>G (p.His831Arg)

gnomAD frequency: 0.00008  dbSNP: rs754324912
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000229569 SCV000288228 uncertain significance Baller-Gerold syndrome 2024-01-26 criteria provided, single submitter clinical testing This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 831 of the RECQL4 protein (p.His831Arg). This variant is present in population databases (rs754324912, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with RECQL4-related conditions. ClinVar contains an entry for this variant (Variation ID: 239734). 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 RECQL4 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.
Baylor Genetics RCV001294206 SCV001483048 uncertain significance Rothmund-Thomson syndrome type 2 2019-01-13 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden RCV003237792 SCV002009911 uncertain significance not provided 2021-11-03 criteria provided, single submitter clinical testing
St. Jude Molecular Pathology, St. Jude Children's Research Hospital RCV001294206 SCV005689259 uncertain significance Rothmund-Thomson syndrome type 2 2024-09-05 criteria provided, single submitter clinical testing The RECQL4 c.2492A>G (p.His831Arg) missense change has a maximum subpopulation frequency of 0.01% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/). In silico tools predict a deleterious effect on protein function, but this prediction has not been confirmed by functional studies. This variant has not been reported in individuals with RECQL4-associated conditions. In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance.

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