Submissions for variant NM_000112.4(SLC26A2):c.2124_2125dup (p.Phe709fs)

dbSNP: rs1554095433

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genetic Services Laboratory, University of Chicago	RCV000501791	SCV000597087	likely pathogenic	not provided	2016-06-16	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001778980	SCV002014889	likely pathogenic	Sulfate transporter-related osteochondrodysplasia	2021-10-12	criteria provided, single submitter	clinical testing	Variant summary: SLC26A2 c.2124_2125dupCT (p.Phe709SerfsX27) results in a premature termination codon, predicted to cause a truncation of the encoded protein. This premature termination is positioned 3 codons away from the last amino acid in the protein (i.e. aa 739). A different variant causing premature termination at the same codon as this variant (i.e. c.2119_2120dupCT, p.Leu708PhefsX28) has been reported in a patient affected with diastrophic dysplasia (PMID: 11241838). The variant allele was found at a frequency of 8.1e-06 in 248236 control chromosomes (gnomAD). To our knowledge, no occurrence of c.2124_2125dupCT in individuals affected with Sulfate Transporter-Related Osteochondrodysplasia and no experimental evidence demonstrating its impact on protein function have been reported. A ClinVar submitter (evaluation after 2014) cites the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001857164	SCV002233884	pathogenic	Achondrogenesis, type IB; Atelosteogenesis type II; Multiple epiphyseal dysplasia type 4; Diastrophic dysplasia	2023-12-30	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Phe709Serfs*27) in the SLC26A2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 31 amino acid(s) of the SLC26A2 protein. This variant is present in population databases (no rsID available, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with SLC26A2-related conditions. ClinVar contains an entry for this variant (Variation ID: 436750). This variant disrupts a region of the SLC26A2 protein in which other variant(s) (p.Ala715Val) have been determined to be pathogenic (PMID: 8571951, 11448940, 15294877, 21077204, 21922596). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.