ClinVar Miner

Submissions for variant NM_005609.4(PYGM):c.1240-2A>G

dbSNP: rs1212333772
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000815772 SCV000956242 likely pathogenic Glycogen storage disease, type V 2024-01-28 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 10 of the PYGM gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in PYGM are known to be pathogenic (PMID: 8316268, 16786513). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with PYGM-related conditions. ClinVar contains an entry for this variant (Variation ID: 658866). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Baylor Genetics RCV000815772 SCV004207216 likely pathogenic Glycogen storage disease, type V 2023-10-15 criteria provided, single submitter clinical testing
Natera, Inc. RCV000815772 SCV002092323 likely pathogenic Glycogen storage disease, type V 2020-08-17 no assertion criteria provided clinical testing
PreventionGenetics, part of Exact Sciences RCV004753050 SCV005354982 likely pathogenic PYGM-related disorder 2024-05-17 no assertion criteria provided clinical testing The PYGM c.1240-2A>G variant is predicted to disrupt the AG splice acceptor site and interfere with normal splicing. This variant has not been reported in the literature. This variant is reported in 0.0030% of alleles in individuals of Latino descent in gnomAD. Variants that disrupt the consensus splice acceptor site in PYGM are expected to be pathogenic. This variant is interpreted as likely pathogenic.

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