ClinVar Miner

Submissions for variant NM_013382.7(POMT2):c.1417C>T (p.Arg473Ter)

gnomAD frequency: 0.00001  dbSNP: rs368817785
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000081565 SCV000113496 pathogenic not provided 2013-06-11 criteria provided, single submitter clinical testing
GeneDx RCV000081565 SCV000196882 pathogenic not provided 2014-06-25 criteria provided, single submitter clinical testing p.Arg473Stop (CGA>TGA): c.1417 C>T in exon 13 of the POMT2 gene (NM_013382.5). The R473X nonsense mutation is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The variant is found in BRAINMALFORMATION panel(s).
Labcorp Genetics (formerly Invitae), Labcorp RCV000705738 SCV000834751 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 2023-10-11 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg473*) in the POMT2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in POMT2 are known to be pathogenic (PMID: 15894594). This variant is present in population databases (rs368817785, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with POMT2-related conditions. ClinVar contains an entry for this variant (Variation ID: 95535). For these reasons, this variant has been classified as Pathogenic.
New York Genome Center RCV000705738 SCV005044152 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 2022-10-21 criteria provided, single submitter clinical testing The c.1417C>T variant in POMT2 has not been reported in heterozygous state in a carrier screening study in a male individual [PMID: 31589614] and it has been deposited in ClinVar [ClinVar ID: 95535] as Pathogenic. The c.1417C>T variant is observed in 5 alleles (~0.0015% % minor allele frequency with 0 homozygotes) in population databases (gnomAD v2.1.1 and v3.1.2, TOPMed Freeze 8, All of Us), suggesting it is not a common benign variant in the populations represented in those databases. The c.1417C>T variant in POMT2 is located in exon 13 of this 21-exon gene, predicted to incorporate a premature termination codon (p.(Arg473Ter)), and is expected to result in loss-of-function via nonsense mediated decay. Multiple loss-of-function variants that are downstream to the c.1417C>T variant have been reported in the literature [PMID: 34413876] and ClinVar [ClinVar ID: 1074015] in individuals with POMT2-related a-dystroglycanopathy. Based on available evidence this inherited c.1417C>T p.(Arg473Ter) variant identified in POMT2 is classified here as Pathogenic.

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