ClinVar Miner

Submissions for variant NM_005199.5(CHRNG):c.753_754del (p.Val253fs) (rs767503038)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000622703 SCV000741891 pathogenic Inborn genetic diseases 2016-12-06 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: POSITIVE: Relevant Alteration(s) Detected
GeneDx RCV000282633 SCV000329801 pathogenic not provided 2018-11-15 criteria provided, single submitter clinical testing The c.753_754delCT pathogenic variant in the CHRNG gene has been reported previously either in the homozygous state or with unknown phase with another CHRNG variant in individuals with lethal and non-lethal autosomal recessive multiple pterygium syndrome (Chong et al., 2015; Vogt et al., 2012; Morgan et al., 2006). The c.753_754delCT has also been observed multiple times with a pathogenic variant on the opposite allele (in trans) in unrelated patients referred for genetic testing at GeneDx. The c.753_754delCT variant causes a frameshift starting with codon Valine 253, changes this amino acid to an Alanine residue, and creates a premature Stop codon at position 44 of the new reading frame, denoted p.Val253AlafsX44. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.753_754delCT variant is observed in 9/34,418 (0.026%) alleles from individuals of Latino background in large population cohorts (Lek et al., 2016). We interpret c.753_754delCT as a pathogenic variant.
Illumina Clinical Services Laboratory,Illumina RCV000778602 SCV000914910 pathogenic CHRNG-Related Disorders 2018-10-26 criteria provided, single submitter clinical testing The CHRNG c.753_754delCT (p.Val253AlafsTer44) variant results in a frameshift, and is predicted to result in premature termination of the protein. This variant has been reported in six studies and is found in a total of seven probands including four in a homozygous state and three in a compound heterozygous state (Morgan et al. 2006; Vogt et al. 2012; Robinson et al. 2013; Chong et al. 2015; Kariminejad et al. 2016; Bayram et al. 2016). The variant has been described in probands with both lethal multiple pterygium syndrome and non-lethal (Escobar) phenotypes. Control data are unavailable for this variant, but it is reported at a frequency of 0.00038 in the African population of the Exome Aggregation Consortium. Based on the evidence, the p.Val253AlafsTer44 variant is classified as pathogenic for CHRNG-related disorders. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
OMIM RCV000020010 SCV000040308 pathogenic Lethal multiple pterygium syndrome 2015-04-01 no assertion criteria provided literature only
OMIM RCV000201795 SCV000256538 pathogenic Multiple pterygium syndrome Escobar type 2015-04-01 no assertion criteria provided literature only

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