ClinVar Miner

Submissions for variant NM_000112.4(SLC26A2):c.1011TGT[3] (p.Val341del) (rs121908077)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000169159 SCV000220386 likely pathogenic Multiple epiphyseal dysplasia type 4 2014-06-05 criteria provided, single submitter literature only
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000355352 SCV000228779 pathogenic not provided 2014-10-14 criteria provided, single submitter clinical testing
GeneDx RCV000355352 SCV000329831 pathogenic not provided 2017-12-29 criteria provided, single submitter clinical testing The c.1020_1022delTGT pathogenic variant was identified in the SLC26A2 gene. It has been published previously in association with SLC26A2-related chondrodysplasias (Pagon RA, et al. 1993; Cai et al.1998; Superti-Furga et al. 1996). The c.1020_1022delTGT is predicted to result in an in-frame deletion of one Valine residue. Functional studies indicate c.1020_1022delTGT results in abnormal sulfate transporter activity (Superti-Furga et al. 1996; Karniski et al. 2004). This variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000586327 SCV000695414 pathogenic Osteochondrodysplasia 2016-07-28 criteria provided, single submitter clinical testing Variant summary: The SLC26A2 c.1020_1022delTGT (p.Val341del) variant involves the deletion of a Valine in the predicted seventh transmembrane domain of the SLC26A2 protein. One in silico tool predicts a damaging outcome for this variant. This variant was found in 17/121404 control chromosomes at a frequency of 0.00014, which does not exceed the estimated maximal expected allele frequency of a pathogenic SLC26A2 variant (0.002958). The variant has been reported in multiple affected individuals in the homozygous and compound heterozygous state, and has been shown to result in impaired ability for sulfate uptake in HEK cells (comparable to negative control cells). In these transfected cells, the protein is not detected by either immunoblot analysis or confocal immunofluorescent microscopy, suggesting that this mutation is either poorly expressed or the protein is rapidly degraded in mammalian cells (Karniski_2004). In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic, and this variant is considered a common disease variant. Taken together, this variant is classified as pathogenic.
Baylor Genetics RCV001004172 SCV001162985 pathogenic Atelosteogenesis type II criteria provided, single submitter clinical testing
Invitae RCV001050109 SCV001214201 likely pathogenic Achondrogenesis, type IB; Atelosteogenesis type II; Multiple epiphyseal dysplasia type 4; Diastrophic dysplasia 2020-10-07 criteria provided, single submitter clinical testing This variant, c.1020_1022del, results in the deletion of 1 amino acid of the SLC26A2 protein (p.Val341del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs777472333, ExAC 0.03%). This variant has been observed in several individuals affected with SLC26A2-related disorders (PMID: 8528239, 9637425, 10482955, 31218223). ClinVar contains an entry for this variant (Variation ID: 65558). This variant has been reported to affect SLC26A2 protein function (PMID:11448940). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
OMIM RCV000023571 SCV000044862 pathogenic Achondrogenesis, type IB 1998-06-16 no assertion criteria provided literature only
GeneReviews RCV000055756 SCV000086696 pathologic Diastrophic dysplasia 2013-07-18 no assertion criteria provided curation Converted during submission to Pathogenic.

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