ClinVar Miner

Submissions for variant NM_014244.5(ADAMTS2):c.673C>T (p.Gln225Ter)

gnomAD frequency: 0.00006  dbSNP: rs137853146
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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000523704 SCV000617793 pathogenic not provided 2021-11-24 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; Reported in ClinVar as pathogenic (ClinVar Variant ID# 5502; Landrum et al., 2016); This variant is associated with the following publications: (PMID: 10417273, 27175728, 26879370, 18973246, 26582918)
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000005837 SCV000699365 pathogenic Ehlers-Danlos syndrome, dermatosparaxis type 2016-02-26 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV000005837 SCV000915129 pathogenic Ehlers-Danlos syndrome, dermatosparaxis type 2018-08-31 criteria provided, single submitter clinical testing The ADAMTS2 c.673C>T (p.Gln225Ter) variant is a stop-gained variant that is predicted to result in a premature termination of the protein. The variant has been reported in a homozygous state in a total of six individuals with Ehlers-Danlos syndrome (Colige et al. 1999; Bar-Yosef et al. 2008). One of the newborn individuals exhibited multiple non-traumatic congenital skull fractures and multiple other defects related to a connective tissue abnormality (Bar-Yosef et al. 2008). Control data are unavailable for the p.Gln225Ter variant, which is reported at a frequency of 0.003053 in the Ashkenazi Jewish population of the Genome Aggregation Database. Due to the potential impact of stop-gained variants and the available evidence, the p.Gln225Ter variant is classified as pathogenic for Ehlers-Danlos syndrome, dermatosparaxis type. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Labcorp Genetics (formerly Invitae), Labcorp RCV000005837 SCV000961901 pathogenic Ehlers-Danlos syndrome, dermatosparaxis type 2024-01-19 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln225*) in the ADAMTS2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ADAMTS2 are known to be pathogenic (PMID: 10417273). This variant is present in population databases (rs137853146, gnomAD 0.3%). This premature translational stop signal has been observed in individuals with Ehlers-Danlos syndrome, type VIIC (PMID: 10417273, 18973246). ClinVar contains an entry for this variant (Variation ID: 5502). For these reasons, this variant has been classified as Pathogenic.
Myriad Genetics, Inc. RCV000005837 SCV001193904 pathogenic Ehlers-Danlos syndrome, dermatosparaxis type 2020-01-03 criteria provided, single submitter clinical testing NM_014244.4(ADAMTS2):c.673C>T(Q225*) is classified as pathogenic in the context of type VIIC Ehlers-Danlos syndrome. Sources cited for classification include the following: PMID 10417273. Classification of NM_014244.4(ADAMTS2):c.673C>T(Q225*) is based on the following criteria: The variant causes a premature termination codon that is expected to be targeted by nonsense-mediated mRNA decay and is reported in individuals with the relevant phenotype. Please note: this variant was assessed in the context of healthy population screening.
Revvity Omics, Revvity RCV000005837 SCV002022231 pathogenic Ehlers-Danlos syndrome, dermatosparaxis type 2021-10-04 criteria provided, single submitter clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV000523704 SCV005413705 pathogenic not provided 2024-02-14 criteria provided, single submitter clinical testing PM3_strong, PS4, PVS1
Fulgent Genetics, Fulgent Genetics RCV000005837 SCV005671644 pathogenic Ehlers-Danlos syndrome, dermatosparaxis type 2024-05-08 criteria provided, single submitter clinical testing
OMIM RCV000005837 SCV000026019 pathogenic Ehlers-Danlos syndrome, dermatosparaxis type 1999-08-01 no assertion criteria provided literature only
Natera, Inc. RCV000005837 SCV001458933 pathogenic Ehlers-Danlos syndrome, dermatosparaxis type 2020-09-16 no assertion criteria provided clinical testing

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