ClinVar Miner

Submissions for variant NM_207122.2(EXT2):c.544C>T (p.Arg182Ter)

dbSNP: rs886039358
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000255822 SCV000321618 pathogenic not provided 2023-10-24 criteria provided, single submitter clinical testing Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 27616605, 30334991, 25525159, 23439489, 10713884, 26961984, 30105120, 23629877, 23262345, 33632255, 32293802, 33414810)
Labcorp Genetics (formerly Invitae), Labcorp RCV000707279 SCV000836369 pathogenic Exostoses, multiple, type 2 2024-11-03 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg182*) in the EXT2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in EXT2 are known to be pathogenic (PMID: 10679937, 19810120). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with hereditary multiple osteochondromatosis (PMID: 10713884, 23262345, 23439489, 23629877, 26961984). Invitae Evidence Modeling of clinical and family history, age, sex, and reported ancestry of multiple individuals with this EXT2 variant has been performed. This variant is expected to be pathogenic with a positive predictive value of at least 99%. This is a validated machine learning model that incorporates the clinical features of 50,122 individuals referred to our laboratory for EXT2 testing. ClinVar contains an entry for this variant (Variation ID: 265133). For these reasons, this variant has been classified as Pathogenic.
CeGaT Center for Human Genetics Tuebingen RCV000255822 SCV001248260 pathogenic not provided 2019-03-01 criteria provided, single submitter clinical testing
Institute of Human Genetics, Heidelberg University RCV000707279 SCV003936059 pathogenic Exostoses, multiple, type 2 2023-06-19 criteria provided, single submitter clinical testing
Neuberg Centre For Genomic Medicine, NCGM RCV000707279 SCV004047704 pathogenic Exostoses, multiple, type 2 criteria provided, single submitter clinical testing The stop gained c.544C>T (p.Arg182Ter) variant has been observed in individuals and families affected with hereditary multiple osteochondromatosis (DobsonStone C et al). The p.Arg182Ter variant is novel (not in any individuals) in gnomAD Exomes and is novel (not in any individuals) in 1000 Genomes. This variant has been submitted to the ClinVar database as Pathogenic. The nucleotide change c.544C>T in EXT2 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. This variant is predicted to cause loss of normal protein function through protein truncation. Loss of function variants have been previously reported to be disease causing. For these reasons, this variant has been classified as Pathogenic.
Juno Genomics, Hangzhou Juno Genomics, Inc RCV004796135 SCV005418319 pathogenic Exostoses, multiple, type 2; Seizures-scoliosis-macrocephaly syndrome criteria provided, single submitter clinical testing PVS1+PM2_Supporting+PS4_Supporting+PP1+PP4

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