ClinVar Miner

Submissions for variant NM_004260.4(RECQL4):c.1573del (p.Cys525fs)

gnomAD frequency: 0.00033  dbSNP: rs386833845
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Total submissions: 16
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV000006438 SCV000596738 pathogenic Rothmund-Thomson syndrome 2017-02-23 criteria provided, single submitter clinical testing
St. Jude Molecular Pathology, St. Jude Children's Research Hospital RCV000761024 SCV000890939 pathogenic B lymphoblastic leukemia lymphoma with t(12;21)(p13;q22); TEL-AML1 (ETV6-RUNX1) 2016-01-15 criteria provided, single submitter clinical testing
St. Jude Molecular Pathology, St. Jude Children's Research Hospital RCV000761053 SCV000890968 pathogenic High grade surface osteosarcoma 2016-07-20 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001582468 SCV001821456 pathogenic Baller-Gerold syndrome; Rapadilino syndrome; Rothmund-Thomson syndrome type 2 2021-07-09 criteria provided, single submitter clinical testing Variant summary: RECQL4 c.1573delT (p.Cys525AlafsX33) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by other laboratories (ClinVar). The variant allele was found at a frequency of 0.00024 in 245124 control chromosomes (gnomAD). c.1573delT has been reported in the literature in multiple individuals affected with RECQL4-Related Disorders (e.g. Siitonen_2009). These data indicate that the variant is very likely to be associated with disease. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
GeneDx RCV001529529 SCV002072823 pathogenic not provided 2022-12-16 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: 31829210, 29367366, 28423363, 12734318, 12838562, 18716613, 15964893, 30947698, 31604778, 29625052, 32081490, 31980526, 31589614, 10678659, 34308104)
CeGaT Center for Human Genetics Tuebingen RCV001529529 SCV002545656 pathogenic not provided 2022-11-01 criteria provided, single submitter clinical testing RECQL4: PVS1, PS4:Moderate
Fulgent Genetics, Fulgent Genetics RCV001582468 SCV002798881 pathogenic Baller-Gerold syndrome; Rapadilino syndrome; Rothmund-Thomson syndrome type 2 2022-03-06 criteria provided, single submitter clinical testing
Ambry Genetics RCV002512832 SCV003682420 pathogenic Inborn genetic diseases 2021-05-21 criteria provided, single submitter clinical testing The c.1573delT (p.C525Afs*33) alteration, located in exon 9 (coding exon 9) of the RECQL4 gene, consists of a deletion of one nucleotide at position 1573, causing a translational frameshift with a predicted alternate stop codon after 33 amino acids. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. This variant has been reported in the homozygous and compound heterozygous states in individuals with RECQL4-related disorders with and without malignancies (Van Maldergem, 2006; Siitonen, 2009). Based on the available evidence, this alteration is classified as pathogenic.
Invitae RCV000169785 SCV004411748 pathogenic Baller-Gerold syndrome 2024-01-25 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Cys525Alafs*33) 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 (rs386833845, gnomAD 0.04%). This premature translational stop signal has been observed in individual(s) with RAPADILINO, Baller-Gerold syndrome, and Rothmund–Thomson syndrome (PMID: 10678659, 12838562, 15897384, 15964893, 18716613, 20113479, 29367366, 31829210). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is also known as g.2886delT. ClinVar contains an entry for this variant (Variation ID: 6066). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000984856 SCV000026621 pathogenic Rothmund-Thomson syndrome type 2 2006-02-01 no assertion criteria provided literature only
Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM) RCV000049813 SCV000082222 probable-pathogenic Rapadilino syndrome no assertion criteria provided not provided Converted during submission to Likely pathogenic.
OMIM RCV000169785 SCV000221750 pathogenic Baller-Gerold syndrome 2006-02-01 no assertion criteria provided literature only
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen RCV001529529 SCV001743119 pathogenic not provided no assertion criteria provided clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ RCV001529529 SCV001956622 pathogenic not provided no assertion criteria provided clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV001529529 SCV001966161 pathogenic not provided no assertion criteria provided clinical testing
GeneReviews RCV000169785 SCV002567920 not provided Baller-Gerold syndrome no assertion provided literature only

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