ClinVar Miner

Submissions for variant NM_014140.3(SMARCAL1):c.863-2A>G (rs761546902)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000797448 SCV000937005 pathogenic Schimke immuno-osseous dysplasia 2020-11-02 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 4 of the SMARCAL1 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 (rs761546902, ExAC 0.02%). This variant has been observed on the opposite chromosome (in trans) from or in combination (phase unknown) with other pathogenic variants in individuals affected with Schimke immuno-osseous dysplasia (PMID: 11799392, 22998683). This finding is consistent with autosomal recessive inheritance, and suggests that this variant contributes to disease. Experimental studies have shown that an individual who carried this sequence change in addition to a second SMARCAL1 sequence change exhibited disrupted elastin expression, however, the functional impact of each variant alone was not assessed (PMID: 22998683). Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in SMARCAL1 are known to be pathogenic (PMID: 11799392, 20301550). For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics,Fulgent Genetics RCV000797448 SCV001752754 pathogenic Schimke immuno-osseous dysplasia 2021-06-30 criteria provided, single submitter clinical testing
Gharavi Laboratory,Columbia University RCV000681817 SCV000809289 pathogenic not provided 2018-09-16 no assertion criteria provided research

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