ClinVar Miner

Submissions for variant NM_000112.3(SLC26A2):c.1957T>A (p.Cys653Ser) (rs104893924)

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Total submissions: 11
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000224702 SCV000280826 pathogenic not provided 2014-10-02 criteria provided, single submitter clinical testing
Counsyl RCV000055760 SCV000487413 likely pathogenic Diastrophic dysplasia 2016-03-11 criteria provided, single submitter clinical testing
Counsyl RCV000004313 SCV000487414 likely pathogenic Multiple epiphyseal dysplasia 4 2016-03-11 criteria provided, single submitter clinical testing
Counsyl RCV000409936 SCV000487415 likely pathogenic Atelosteogenesis type 2 2016-03-11 criteria provided, single submitter clinical testing
Counsyl RCV000411019 SCV000487416 likely pathogenic Achondrogenesis, type IB 2016-03-11 criteria provided, single submitter clinical testing
Division of Human Genetics,Children's Hospital of Philadelphia RCV000477884 SCV000536907 likely pathogenic Achondrogenesis, type IB; Atelosteogenesis type 2; Multiple epiphyseal dysplasia 4; Diastrophic dysplasia 2016-08-13 no assertion criteria provided research
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000224702 SCV000228778 pathogenic not provided 2014-10-14 criteria provided, single submitter clinical testing
GeneReviews RCV000055760 SCV000086700 pathologic Diastrophic dysplasia 2013-07-18 no assertion criteria provided curation Converted during submission to Pathogenic.
Integrated Genetics/Laboratory Corporation of America RCV000780712 SCV000918219 pathogenic Osteochondrodysplasia 2018-06-07 criteria provided, single submitter clinical testing Variant summary: SLC26A2 c.1957T>A (p.Cys653Ser) results in a non-conservative amino acid change located in the STAS domain of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00013 in 276994 control chromosomes (gnomAD). The variant, c.1957T>A, has been reported in the literature in multiple homozygote and compound heterozygote individuals affected with recessive Multiple epiphyseal dysplasia (Ballhausen_2003, Jackson_2012). These data indicate that the variant is very likely to be associated with disease. A functional study, Karniski_2004, found the variant to have ~55% stimulated sulfate transport. Two ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cite the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Invitae RCV000477884 SCV000952836 pathogenic Achondrogenesis, type IB; Atelosteogenesis type 2; Multiple epiphyseal dysplasia 4; Diastrophic dysplasia 2018-10-19 criteria provided, single submitter clinical testing This sequence change replaces cysteine with serine at codon 653 of the SLC26A2 protein (p.Cys653Ser). The cysteine residue is highly conserved and there is a moderate physicochemical difference between cysteine and serine. This variant is present in population databases (rs104893924, ExAC 0.02%). This variant has been observed to be homozygous or in combination with another SLC26A2 variant in individuals affected with diastrophic dysplasia and epiphyseal dysplasia, and has been shown to segregate with disease in several families (PMID: 12966518, 21077204, 20525296, 11241838). ClinVar contains an entry for this variant (Variation ID: 4098). Experimental studies have shown that this missense change causes reduced protein function (PMID: 15294877). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000004313 SCV000024484 pathogenic Multiple epiphyseal dysplasia 4 2003-10-15 no assertion criteria provided literature only

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