ClinVar Miner

Submissions for variant NM_004260.4(RECQL4):c.2704C>T (p.Arg902Trp)

gnomAD frequency: 0.00001  dbSNP: rs761231404
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000527753 SCV000631114 uncertain significance Baller-Gerold syndrome 2023-11-08 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 902 of the RECQL4 protein (p.Arg902Trp). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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: 459424). 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.
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden RCV003237906 SCV002009907 uncertain significance not provided 2021-11-03 criteria provided, single submitter clinical testing
Laboratory of Molecular Epidemiology of Birth Defects, West China Second University Hospital, Sichuan University RCV003153690 SCV003843643 likely pathogenic Ovarian cancer 2022-01-01 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV004527637 SCV004104806 uncertain significance RECQL4-related disorder 2023-01-17 criteria provided, single submitter clinical testing The RECQL4 c.2704C>T variant is predicted to result in the amino acid substitution p.Arg902Trp. This variant was reported in an individual with sporadic breast cancer (Table 2, Moradian et al. 2021. PubMed ID: 33558524). This variant is reported in 0.0011% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/8-145738281-G-A) and is interpreted as a variant of uncertain significance in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/459424). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Center of Medical Genetics and Primary Health Care RCV001269499 SCV001449048 uncertain significance Malignant tumor of breast no assertion criteria provided clinical testing

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