ClinVar Miner

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

gnomAD frequency: 0.00008  dbSNP: rs137852927
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Total submissions: 6
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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 2024-01-21 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. Loss-of-function variants in EVC2 are known to be pathogenic (PMID: 17024374, 19810119, 19876929). This variant is present in population databases (rs137852927, gnomAD 0.2%). This premature translational stop signal has been observed in individual(s) with autosomal recessive Ellis-van Creveld syndrome (PMID: 12468274, 23220543). This variant is also known as C3754T (Q1009X). ClinVar contains an entry for this variant (Variation ID: 3386). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
Laboratory for Molecular Medicine, Mass General Brigham 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 Genetics, 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.
Ambry Genetics RCV001265673 SCV001443840 pathogenic Inborn genetic diseases 2017-12-18 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV000799858 SCV002813111 pathogenic Ellis-van Creveld syndrome; Curry-Hall syndrome 2022-01-06 criteria provided, single submitter clinical testing
OMIM RCV000003553 SCV000023711 pathogenic Ellis-van Creveld syndrome 2002-12-01 no assertion criteria provided literature only

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