ClinVar Miner

Submissions for variant NM_000441.2(SLC26A4):c.-4+5G>A

gnomAD frequency: 0.00006  dbSNP: rs727503425
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000151882 SCV000200378 likely pathogenic Rare genetic deafness 2014-06-17 criteria provided, single submitter clinical testing The -4+5G>A variant in SLC26A4 has been identified in one individual with hearin g loss and EVA by our laboratory (LMM unpublished data) likely in trans with an other pathogenic variant SLC26A4 variant. In addition, this variant has not bee n identified in large population studies and is located in the 5' splice region. Computational tools suggest a possible impact to splicing; though this informat ion is not predictive enough to determine pathogenicity. In summary, this varia nt is likely pathogenic.
King Laboratory, University of Washington RCV003230418 SCV003844110 likely pathogenic Autosomal recessive nonsyndromic hearing loss 4 2023-02-28 criteria provided, single submitter research This variant was found in compound heterozygosity with an SLC26A4 splicing variant that is known to be pathogenic, in a patient with bilateral sensorineural hearing loss of onset <18 years, in a study of pediatric hearing loss conducted by the King Laboratory (Carlson RJ et al. JAMA-OtoHNS 2023). This patient's family has no history of childhood-onset hearing loss. This variant is a single base pair substitution within the 5’ UTR that is predicted to interfere with normal splicing. As of January 2023, this variant has been reported to ClinVar as likely pathogenic and is found in 2 heterozygotes on gnomAD. Based on compound heterozygosity with a loss-of-function variant, consistently predicted functional effect, and goodness of fit of genotype to phenotype, we conclude that this variant is likely pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003226214 SCV003922666 uncertain significance not specified 2023-03-24 criteria provided, single submitter clinical testing

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