ClinVar Miner

Submissions for variant NM_002863.5(PYGL):c.1518G>A (p.Glu506=)

dbSNP: rs748519147
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000700937 SCV000829715 uncertain significance Glycogen storage disease, type VI 2021-12-24 criteria provided, single submitter clinical testing In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 578046). This variant has been observed in individuals with clinical features of glycogen storage disease type VI (PMID: 25266922; Invitae). This variant is present in population databases (rs748519147, gnomAD 0.02%). This sequence change affects codon 506 of the PYGL mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the PYGL protein. This variant also falls at the last nucleotide of exon 12, which is part of the consensus splice site for this exon.
3billion RCV000700937 SCV002318864 uncertain significance Glycogen storage disease, type VI 2022-03-22 criteria provided, single submitter clinical testing The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency:0.0000239). In silico tools predict the variant to alter splicing and produce an abnormal transcript (SPLICEAI: 0.88>=0.8). Therefore, this variant is classified as uncertain significance according to the recommendation of ACMG/AMP guideline.

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