ClinVar Miner

Submissions for variant NM_000112.3(SLC26A2):c.1707C>G (p.Tyr569Ter) (rs766836061)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000588352 SCV000695415 likely pathogenic Osteochondrodysplasia 2017-07-14 criteria provided, single submitter clinical testing Variant summary: The SLC26A2 c.1707C>G (p.Tyr569X) variant results in a premature termination codon, predicted to cause a truncated or absent SLC26A2 protein due to nonsense mediated decay, which are commonly known mechanisms for disease. A truncation downstream of this position have been classified as pathogenic by our laboratory (e.g. c.1724delA (p.Lys575fsX10)). This variant is absent in 121148 control chromosomes (ExAC). The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as likely pathogenic.
Invitae RCV000809074 SCV000949213 pathogenic Achondrogenesis, type IB; Atelosteogenesis type II; Multiple epiphyseal dysplasia type 4; Diastrophic dysplasia 2018-11-26 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the SLC26A2 gene (p.Tyr569*). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 171 amino acids of the SLC26A2 protein. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with SLC26A2-related disease. ClinVar contains an entry for this variant (Variation ID: 495551). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. This variant disrupts the C-terminus of the SLC26A2 protein. Other variant(s) that disrupt this region (p.Lys575Serfs*10) have been determined to be pathogenic (PMID: 8571951, 8528239). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic.

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