ClinVar Miner

Submissions for variant NM_018972.4(GDAP1):c.311-1G>A

gnomAD frequency: 0.00001  dbSNP: rs1370011538
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001390388 SCV001592107 pathogenic Charcot-Marie-Tooth disease type 4A 2023-09-21 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 2 of the GDAP1 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 GDAP1 are known to be pathogenic (PMID: 11743580). 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. ClinVar contains an entry for this variant (Variation ID: 637452). Disruption of this splice site has been observed in individuals with autosomal recessive Charcot-Marie-Tooth disease (PMID: 15944907, 18812441). This variant is present in population databases (no rsID available, gnomAD 0.0009%).
CeGaT Center for Human Genetics Tuebingen RCV001726328 SCV001962140 pathogenic not provided 2021-07-01 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV004527815 SCV004110684 likely pathogenic GDAP1-related disorder 2023-02-27 criteria provided, single submitter clinical testing The GDAP1 c.311-1G>A variant is predicted to disrupt the AG splice acceptor site and interfere with normal splicing. This variant was reported in the compound heterozygous state in a patient with Charcot-Marie-Tooth disease (Kabzinska et al. 2005. PubMed ID: 15944907). This variant is reported in 0.00088% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/8-75272371-G-A). Variants that disrupt the consensus splice acceptor site in GDAP1 are expected to be pathogenic. This variant is interpreted as likely pathogenic.
Fulgent Genetics, Fulgent Genetics RCV005047050 SCV005679119 likely pathogenic Charcot-Marie-Tooth disease axonal type 2K; Charcot-Marie-Tooth disease type 4A; Charcot-Marie-Tooth disease, axonal, with vocal cord paresis, autosomal recessive; Charcot-Marie-Tooth disease recessive intermediate A 2024-02-15 criteria provided, single submitter clinical testing
Inherited Neuropathy Consortium RCV000789640 SCV000929012 uncertain significance Charcot-Marie-Tooth disease no assertion criteria provided literature only
Inherited Neuropathy Consortium Ii, University Of Miami RCV003447230 SCV004174646 uncertain significance Charcot-Marie-Tooth disease axonal type 2K 2016-01-06 no assertion criteria provided literature only

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