ClinVar Miner

Submissions for variant NM_004260.4(RECQL4):c.1048_1049del (p.Arg350fs)

gnomAD frequency: 0.00013  dbSNP: rs746636748
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Total submissions: 11
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000178888 SCV000231061 pathogenic not provided 2014-09-03 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000471676 SCV000546005 pathogenic Baller-Gerold syndrome 2024-12-04 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg350Glyfs*21) in the RECQL4 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in RECQL4 are known to be pathogenic (PMID: 12734318, 12952869). This variant is present in population databases (rs746636748, gnomAD 0.02%). This premature translational stop signal has been observed in individual(s) with Rothmund-Thomson syndrome (PMID: 12734318, 18716613, 21143835, 25120469, 28039508). This variant is also known as g.1798delAG. ClinVar contains an entry for this variant (Variation ID: 197759). For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV000178888 SCV001813073 pathogenic not provided 2025-02-14 criteria provided, single submitter clinical testing Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 29642415, 34426522, 31589614, 18504617, 25120469, 29625052, 33718801, 21143835, 35346574, 36451132, 18716613, 28492532, 32769558, 12734318, 28039508, 27247962, 34964962)
Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center RCV001814092 SCV002061486 likely pathogenic Rothmund-Thomson syndrome type 2 2021-07-15 criteria provided, single submitter clinical testing PVS1, PM2
St. Jude Molecular Pathology, St. Jude Children's Research Hospital RCV001814092 SCV002584641 pathogenic Rothmund-Thomson syndrome type 2 2022-09-21 criteria provided, single submitter clinical testing The RECQL4 c.1048_1049del (p.Arg350GlyfsTer21) change removes two nucleotides to cause a frameshift and the creation of a premature stop codon. This change is predicted to cause protein truncation or absence of the protein due to nonsense mediated decay. This variant has a maximum subpopulation frequency of 0.021% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/). This variant has been reported in the literature as compound heterozygous in individuals with Rothmund–Thomson syndrome (PMID: 18716613, 21143835, 25120469, 28039508). In summary, this variant meets criteria to be classified as pathogenic.
Fulgent Genetics, Fulgent Genetics RCV002503690 SCV002814690 pathogenic Baller-Gerold syndrome; Rapadilino syndrome; Rothmund-Thomson syndrome type 2 2022-04-07 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV000178888 SCV004159660 pathogenic not provided 2024-05-01 criteria provided, single submitter clinical testing RECQL4: PVS1, PM2, PM3
Juno Genomics, Hangzhou Juno Genomics, Inc RCV001814092 SCV005415970 pathogenic Rothmund-Thomson syndrome type 2 criteria provided, single submitter clinical testing PM2_Supporting+PVS1+PM3_VeryStrong+PP1_Moderate
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) RCV000178888 SCV001800461 pathogenic not provided no assertion criteria provided clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ RCV000178888 SCV001956285 pathogenic not provided no assertion criteria provided clinical testing
PreventionGenetics, part of Exact Sciences RCV004737282 SCV005358536 pathogenic RECQL4-related disorder 2024-09-12 no assertion criteria provided clinical testing The RECQL4 c.1048_1049delAG variant is predicted to result in a frameshift and premature protein termination (p.Arg350Glyfs*21). This variant has been reported in the compound heterozygous state in individuals with Rothmund Thomson Syndrome (RTS) (Reported as g.1798delAG, Wang et al 2003. PubMed ID: 12734318; Siitonen et al. 2008. PubMed ID: 18716613; De Somer et al. 2010. PubMed ID: 21143835; Guerrero-González et al. 2014. PubMed ID: 25120469; van Rij MC et al 2016. PubMed ID: 28039508). This variant is reported in 0.021% of alleles in individuals of African descent in gnomAD. Frameshift variants in RECQL4 are expected to be pathogenic. This variant is interpreted as pathogenic.

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