ClinVar Miner

Submissions for variant NM_001378615.1(CC2D2A):c.1340C>T (p.Ala447Val)

gnomAD frequency: 0.00004  dbSNP: rs775138548
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001239571 SCV001412454 uncertain significance Familial aplasia of the vermis; Meckel-Gruber syndrome 2022-08-23 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 447 of the CC2D2A protein (p.Ala447Val). This variant is present in population databases (rs775138548, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with CC2D2A-related conditions. ClinVar contains an entry for this variant (Variation ID: 965184). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt CC2D2A protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ocular Genomics Institute, Massachusetts Eye and Ear RCV001376531 SCV001573709 uncertain significance Joubert syndrome 9 2021-04-08 criteria provided, single submitter research The CC2D2A c.1340C>T variant was identified in an individual with retinitis pigmentosa with a presumed recessive inheritance pattern. Through a review of available evidence we were able to apply the following criteria: PM2. Based on this evidence we have classified this variant as Variant of Uncertain Significance.
GeneDx RCV002464415 SCV002759063 uncertain significance not provided 2022-12-02 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on splicing.; In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Fulgent Genetics, Fulgent Genetics RCV005029817 SCV005660535 uncertain significance Meckel syndrome, type 6; Joubert syndrome 9; COACH syndrome 2; Retinitis pigmentosa 93 2024-02-21 criteria provided, single submitter clinical testing

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