ClinVar Miner

Submissions for variant NM_147127.5(EVC2):c.3265C>T (p.Gln1089Ter) (rs137852927)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000799858 SCV000939540 pathogenic Ellis-van Creveld syndrome; Curry-Hall syndrome 2019-12-24 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln1089*) in the EVC2 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs137852927, ExAC 0.01%). This variant has been observed in individuals affected with autosomal recessive Ellis-van Creveld syndrome (PMID: 12468274, 23220543). This variant is also known as C3754T (Q1009X) in the literature. ClinVar contains an entry for this variant (Variation ID: 3386). Loss-of-function variants in EVC2 are known to be pathogenic (PMID: 17024374, 19810119, 19876929). For these reasons, this variant has been classified as Pathogenic.
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000003553 SCV000967782 pathogenic Ellis-van Creveld syndrome 2018-10-10 criteria provided, single submitter clinical testing The p.Gln1089X variant in EVC2 has been reported in the homozygous state in one individual with Ellis-van Creveld syndrome (Galdzicka 2002). It has also been id entified in 0.15% (15/9850) of European chromosomes by gnomAD (http://gnomad.bro adinstitute.org). This nonsense variant leads to a premature termination codon a t position 1089, which is predicted to lead to a truncated or absent protein. Bi allelic loss of function variants in EVC2 have been reported as disease causing in several individuals with Ellis-van Creveld syndrome. In summary, this variant meets criteria to be classified as pathogenic for autosomal recessive Ellis-van Creveld syndrome based on a case observation and the predicted impact on the pr otein. ACMG/AMP criteria applied: PVS1, PP4, PM3_Supporting.
Myriad Women's Health, Inc. RCV000003553 SCV001193772 pathogenic Ellis-van Creveld syndrome 2019-12-20 criteria provided, single submitter clinical testing NM_147127.4(EVC2):c.3265C>T(Q1089*) is classified as pathogenic in the context of EVC2-related Ellis-van Creveld syndrome. Sources cited for classification include the following: PMID 23220543 and 12468274. Classification of NM_147127.4(EVC2):c.3265C>T(Q1089*) 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.
OMIM RCV000003553 SCV000023711 pathogenic Ellis-van Creveld syndrome 2002-12-01 no assertion criteria provided literature only

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