ClinVar Miner

Submissions for variant NM_014140.4(SMARCAL1):c.2070+2dup

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001386134 SCV001586260 pathogenic Schimke immuno-osseous dysplasia 2020-09-09 criteria provided, single submitter clinical testing This sequence change falls in intron 12 of the SMARCAL1 gene. It does not directly change the encoded amino acid sequence of the SMARCAL1 protein, but it affects a nucleotide within the consensus splice site of the intron. This variant is present in population databases (rs762716070, ExAC 0.003%). This variant has been observed in individual(s) with clinical features of Schimke immuno-osseous dysplasia (PMID: 25943327, 30784191, 27577878). It has also been observed to segregate with disease in related individuals. This variant is also known as c.2070+2insT and c.2070+2_3insT in the literature. Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Experimental studies have shown that this variant results in exon 12 skipping (PMID: 25943327, 27577878). This variant disrupts the p.Arg645Cys amino acid residue (located in exon 12) in SMARCAL1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 22998683, 11799392, 25748404). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.

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