ClinVar Miner

Submissions for variant NM_000441.2(SLC26A4):c.165-1G>A (rs759792660)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
NxGen MDx RCV001027888 SCV001167353 likely pathogenic Pendred syndrome 2019-11-26 criteria provided, single submitter clinical testing This is a predicted null variant in a splice site (PVS1). The GnomAD exomes allele frequency = 0.0000477 is less than 0.0001 threshold for the recessive gene, SLC26A4 (good GnomAD exomes coverage = 93.2), and the variant is not found in GnomAD genomes (PM2). Variant cited as pathogenic in PMIDs: 28964290 and 11748854. Predicted pathogenic in computational models (DANN, EIGEN, FATHMM-MKL and MutationTaster) with no benign predictions (PP3).
Invitae RCV001060495 SCV001225188 pathogenic not provided 2020-08-25 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 2 of the SLC26A4 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is present in population databases (rs759792660, ExAC 0.07%). This variant has been observed to segregate with Pendred syndrome (PMID: 11375792). This variant is also known as IVS2-1G>A in the literature. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in SLC26A4 are known to be pathogenic (PMID: 16283880, 25394566, 26252218, 26445815). For these reasons, this variant has been classified as Pathogenic.

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