ClinVar Miner

Submissions for variant NM_014140.4(SMARCAL1):c.250dup (p.Gln84fs)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Victorian Clinical Genetics Services,Murdoch Childrens Research Institute RCV001089943 SCV001244988 likely pathogenic Schimke immuno-osseous dysplasia 2018-08-04 criteria provided, single submitter clinical testing A heterozygous duplication variant, NM_014140.3(SMARCAL1):c.250dup, has been identified in exon 3 of 18 of the SMARCAL1 gene. This duplication is predicted to create a frameshift starting at amino acid position 84, introducing a stop codon 5 residues downstream (NM_014140.3(SMARCAL1):p.(Gln84Profs*5)). This variant is predicted to result in loss of protein function through nonsense-mediated decay (NMD), which is a reported mechanism of pathogenicity for this gene. However, truncation of the protein as a result of a NMD-escape mechanism has not been excluded. The variant is absent in population databases (gnomAD, dbSNP, 1000G). In addition, multiple variants resulting in a premature stop codon have been previously described as disease causing. Analysis of parental samples indicated this variant was maternally inherited. Based on the information available at the time of curation, this variant has been classified as LIKELY PATHOGENIC.

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