ClinVar Miner

Submissions for variant NM_013382.7(POMT2):c.1997A>G (p.Tyr666Cys)

gnomAD frequency: 0.00010  dbSNP: rs200198778
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Total submissions: 12
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000081569 SCV000196887 pathogenic not provided 2020-08-06 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 17634419, 30060766, 24002165, 19299310, 28980384, 29175898, 17878207, 19138766, 17869517, 27854218, 32115343, 31127727, 31589614, 32528171)
Genetic Services Laboratory, University of Chicago RCV000193219 SCV000248592 pathogenic Muscular dystrophy 2015-07-01 criteria provided, single submitter clinical testing
Center for Genetic Medicine Research, Children's National Medical Center RCV000003376 SCV000265767 likely pathogenic Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B2 2015-12-01 criteria provided, single submitter research
Eurofins Ntd Llc (ga) RCV000081569 SCV000331113 pathogenic not provided 2017-01-15 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV000515301 SCV000611299 pathogenic Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A1; Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A2; Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B2; Autosomal recessive limb-girdle muscular dystrophy type 2N 2021-08-09 criteria provided, single submitter clinical testing
Invitae RCV000648175 SCV000769989 pathogenic Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A2; Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B2; Autosomal recessive limb-girdle muscular dystrophy type 2N 2024-01-18 criteria provided, single submitter clinical testing This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 666 of the POMT2 protein (p.Tyr666Cys). This variant is present in population databases (rs200198778, gnomAD 0.02%). This missense change has been observed in individuals with congenital muscular dystrophy (PMID: 17634419, 17878297, 24002165). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 3221). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt POMT2 protein function with a positive predictive value of 80%. For these reasons, this variant has been classified as Pathogenic.
SIB Swiss Institute of Bioinformatics RCV000003376 SCV000803551 likely pathogenic Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B2 2018-05-31 criteria provided, single submitter curation This variant is interpreted as a Likely Pathogenic, for Muscular dystrophy-dystroglycanopathy (congenital with mental retardation), type B, 2, in Autosomal Recessive manner. The following ACMG Tag(s) were applied: PP3 => Multiple lines of computational evidence support a deleterious effect on the gene or gene product. PM3 => For recessive disorders, detected in trans with a pathogenic variant (PMID:17634419,19138766). PP1 => Cosegregation with disease in multiple affected family members in a gene definitively known to cause the disease (PMID:17878207). PM2 => Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium. PS4-Moderate => Found in multiple unrelated patients (PMID:17878207,17634419,19138766,19299310).
Revvity Omics, Revvity RCV000081569 SCV002019498 pathogenic not provided 2022-05-26 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV003398429 SCV004104804 pathogenic POMT2-related disorder 2023-03-14 criteria provided, single submitter clinical testing The POMT2 c.1997A>G variant is predicted to result in the amino acid substitution p.Tyr666Cys. This variant has been reported in the homozygous or compound heterozygous state in many individuals with POMT2-related disorders (Yanagisawa et al. 2007. PubMed ID: 17634419; Godfrey et al. 2007. PubMed ID: 17878207; Martinez et al. 2013. PubMed ID: 24002165; Østergaard et al. 2017. PubMed ID: 29175898; Westra et al. 2019. PubMed ID: 31127727; Saat et al. 2021. PubMed ID: 33963534; Punetha et al. 2016. PubMed ID: 27854218). This variant is reported in 0.016% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/14-77745107-T-C). This variant is interpreted as pathogenic.
Baylor Genetics RCV000003377 SCV004204084 pathogenic Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A2 2023-10-30 criteria provided, single submitter clinical testing
OMIM RCV000003376 SCV000023534 pathogenic Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B2 2009-07-01 no assertion criteria provided literature only
OMIM RCV000003377 SCV000023535 pathogenic Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A2 2009-07-01 no assertion criteria provided literature only

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