ClinVar Miner

Submissions for variant NM_032444.4(SLX4):c.2137C>T (p.Arg713Ter)

gnomAD frequency: 0.00001  dbSNP: rs760126773
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000630869 SCV000751840 pathogenic Fanconi anemia 2022-12-04 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 526348). This variant has not been reported in the literature in individuals affected with SLX4-related conditions. This variant is present in population databases (rs760126773, gnomAD 0.007%). This sequence change creates a premature translational stop signal (p.Arg713*) in the SLX4 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SLX4 are known to be pathogenic (PMID: 21240277).
Baylor Genetics RCV001788304 SCV002030142 pathogenic Fanconi anemia complementation group P 2021-07-23 criteria provided, single submitter clinical testing This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868].
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV001788304 SCV002495965 likely pathogenic Fanconi anemia complementation group P 2021-11-03 criteria provided, single submitter clinical testing SLX4 NM_032444.2 exon 10 p.Arg713* (c.2137C>T): This variant has not been reported in the literature is association with SLX4-related disease, but is present in 0.001% (1/68026) of European alleles in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/16-3594476-G-A?dataset=gnomad_r3). Please note, disease causing variants may be present in control databases at low frequencies, reflective of the general population, carrier status, and/or variable expressivity. This variant is present in ClinVar (Variation ID:526348). Evolutionary conservation and computational predictive tools for this variant are limited or unavailable. This variant creates a premature stop at this codon which results in an absent or abnormal protein. Loss of function variants have been reported in association with disease for this gene (Stoepker 2011 PMID:21240277). In summary, data on this variant is highly suspicious for disease, but requires further evidence for pathogenicity. Therefore, this variant is classified as likely pathogenic.
GeneDx RCV003126875 SCV003803475 likely pathogenic not provided 2022-08-15 criteria provided, single submitter clinical testing Nonsense 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; Observed in 1/5951 cases and 1/6115 controls in an ovarian cancer study (Song et al., 2021); This variant is associated with the following publications: (PMID: 26689913, 32546565)

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