ClinVar Miner

Submissions for variant NM_207122.2(EXT2):c.1945C>T (p.Arg649Ter)

gnomAD frequency: 0.00004  dbSNP: rs765648513
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001039837 SCV001203386 pathogenic Exostoses, multiple, type 2 2024-01-18 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg649*) 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 present in population databases (rs765648513, gnomAD 0.007%). This premature translational stop signal has been observed in individual(s) with multiple osteochondromas (PMID: 19344451). ClinVar contains an entry for this variant (Variation ID: 838313). For these reasons, this variant has been classified as Pathogenic.
CeGaT Center for Human Genetics Tuebingen RCV001091959 SCV001248263 likely pathogenic not provided 2022-08-01 criteria provided, single submitter clinical testing EXT2: PVS1, PS4:Supporting
Illumina Laboratory Services, Illumina RCV001039837 SCV001259402 uncertain significance Exostoses, multiple, type 2 2018-07-26 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
GeneDx RCV001091959 SCV001763799 likely pathogenic not provided 2021-12-29 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; This variant is associated with the following publications: (PMID: 29625052, 25525159, 19344451, 26689913)
Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center RCV002221603 SCV002499171 likely pathogenic Exostoses, multiple, type 2; Seizures-scoliosis-macrocephaly syndrome 2022-01-11 criteria provided, single submitter clinical testing PVS1, PM2, PS4_Supporiting
St. Jude Molecular Pathology, St. Jude Children's Research Hospital RCV001039837 SCV004031175 likely pathogenic Exostoses, multiple, type 2 2023-05-31 criteria provided, single submitter clinical testing The EXT2 c.2044C>T (p.Arg682Ter) change is a nonsense variant that is predicted to cause premature protein truncation or absence of protein due to nonsense-mediated decay. This variant has been reported in an individual with multiple osteochondromas (PMID: 19344451). This variant has a maximum subpopulation frequency of 0.006% in gnomAD v2.1.1. This variant corresponds to NM_207122.1:c.1945C>T (p.Arg649Ter) in the MANE select transcript. In summary, this variant meets criteria to be classified as likely pathogenic. 
Baylor Genetics RCV001039837 SCV004192785 pathogenic Exostoses, multiple, type 2 2023-10-22 criteria provided, single submitter clinical testing

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