ClinVar Miner

Submissions for variant NM_153700.2(STRC):c.4219-1G>A

gnomAD frequency: 0.00006  dbSNP: rs748854592
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Total submissions: 5
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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 RCV000604175 SCV000712640 pathogenic Rare genetic deafness 2020-03-16 criteria provided, single submitter clinical testing The c.4219-1G>A variant in STRC has been previously reported by our laboratory in 1 individual with hearing loss who was compound heterozygous for a second truncating STRC variant, though phase was not confirmed. This variant has been identified in 0.01% (4/24064) of Finnish chromosomes by gnomAD (http://gnomad.broadinstitute.org). This variant occurs within the canonical splice site (+/- 1,2) and is predicted to cause altered splicing leading to an abnormal or absent protein. Loss of function of the STRC gene is an established disease mechanism in autosomal recessive sensorineural hearing loss. In summary, this variant meets criteria to be classified as pathogenic for autosomal recessive sensorineural hearing loss. ACMG/AMP Criteria applied: ACMG/AMP criteria applied: PVS1, PM2_Supporting, PM3_Supporting.
Fulgent Genetics, Fulgent Genetics RCV000763351 SCV000894041 likely pathogenic Deafness-infertility syndrome; Autosomal recessive nonsyndromic hearing loss 16; Spermatogenic failure 7 2018-10-31 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV002467922 SCV002762977 likely pathogenic Autosomal recessive nonsyndromic hearing loss 16 criteria provided, single submitter clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV003480711 SCV004225750 likely pathogenic not provided 2022-05-31 criteria provided, single submitter clinical testing PM2, PVS1
PreventionGenetics, part of Exact Sciences RCV003953009 SCV004770866 likely pathogenic STRC-related disorder 2024-02-20 no assertion criteria provided clinical testing The STRC c.4219-1G>A variant is predicted to disrupt the AG splice acceptor site and interfere with normal splicing. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.017% of alleles in individuals of European (Finnish) descent in gnomAD. Variants that disrupt the consensus splice acceptor site in STRC are expected to be pathogenic. This variant is interpreted as likely pathogenic.

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