ClinVar Miner

Submissions for variant NM_013339.4(ALG6):c.796_799dup (p.Asp267delinsGlyTer)

dbSNP: rs2100421727
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV001817831 SCV002069292 likely pathogenic not provided 2018-12-14 criteria provided, single submitter clinical testing DNA sequence analysis of the ALG6 gene demonstrated a 4 base pair duplication in exon 9, c.796_799dup. This duplication is predicted to result in an amino acid frameshift and create a premature stop codon 3 amino acids downstream of the sequence change, p.Asp267Glyfs*2. This sequence change is predicted to result in an abnormal transcript, which may be degraded, or may lead to the production of a truncated ALG6 protein with potentially abnormal function. While this duplication has not previously been described in the literature, other frameshift mutations in the ALG6 gene have been described in some patients with ALG6-related congenital disorder of glycosylation (PMID: 23430515). The c.796_799dup sequence change has not been reported in the EXAC or gnomAD population databases. Based on the above information, we classify this variant as a likely pathogenic variant.
Invitae RCV002545184 SCV003254334 pathogenic ALG6-congenital disorder of glycosylation 1C 2022-05-21 criteria provided, single submitter clinical testing ClinVar contains an entry for this variant (Variation ID: 1338460). For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This variant has not been reported in the literature in individuals affected with ALG6-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Asp267Glyfs*2) in the ALG6 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ALG6 are known to be pathogenic (PMID: 19862844).
Baylor Genetics RCV002545184 SCV004199722 likely pathogenic ALG6-congenital disorder of glycosylation 1C 2022-11-15 criteria provided, single submitter clinical testing

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