ClinVar Miner

Submissions for variant NM_000112.4(SLC26A2):c.485_486del (p.Val162fs) (rs763198695)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000411191 SCV000487731 likely pathogenic Diastrophic dysplasia 2016-10-04 criteria provided, single submitter clinical testing
Counsyl RCV000409216 SCV000487732 likely pathogenic Multiple epiphyseal dysplasia type 4 2016-10-04 criteria provided, single submitter clinical testing
Counsyl RCV000410244 SCV000487733 likely pathogenic Atelosteogenesis type II 2016-10-04 criteria provided, single submitter clinical testing
Counsyl RCV000411337 SCV000487734 likely pathogenic Achondrogenesis, type IB 2016-10-04 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000780713 SCV000918220 pathogenic Osteochondrodysplasia 2020-09-09 criteria provided, single submitter clinical testing Variant summary: SLC26A2 c.485_486delTG (p.Val162GlyfsX12) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 4e-06 in 247972 control chromosomes. c.485_486delTG has been reported in the literature in at-least one individual affected with Sulfate Transporter-Related Osteochondrodysplasia and has been subsequently cited by others (example, Cho_2010, Kim_2011, Bae_2016, Kausar_2019) consistent with the mutational spectrum of SLC26A2 related skeletal dysplasias. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Invitae RCV001041550 SCV001205174 pathogenic Achondrogenesis, type IB; Atelosteogenesis type II; Multiple epiphyseal dysplasia type 4; Diastrophic dysplasia 2020-08-29 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Val162Glyfs*12) in the SLC26A2 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs763198695, ExAC 0.01%). This variant has been observed in individuals affected with SLC26A2-related skeletal dysplasia (PMID: 20592910, Invitae). ClinVar contains an entry for this variant (Variation ID: 371777). Loss-of-function variants in SLC26A2 are known to be pathogenic (PMID: 7923357, 8528239, 8571951, 10482955, 11241838, 12525546, 20592910, 21077202). For these reasons, this variant has been classified as Pathogenic.

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