ClinVar Miner

Submissions for variant NM_001378615.1(CC2D2A):c.4340A>C (p.Glu1447Ala)

gnomAD frequency: 0.00004  dbSNP: rs387907058
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000594523 SCV000704957 uncertain significance not provided 2017-01-25 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001852033 SCV002184690 uncertain significance Familial aplasia of the vermis; Meckel-Gruber syndrome 2022-04-29 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with alanine, which is neutral and non-polar, at codon 1447 of the CC2D2A protein (p.Glu1447Ala). This variant is present in population databases (rs387907058, gnomAD 0.005%). 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: 30934). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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.
PreventionGenetics, part of Exact Sciences RCV004532401 SCV004119343 uncertain significance CC2D2A-related disorder 2023-07-21 criteria provided, single submitter clinical testing The CC2D2A c.4340A>C variant is predicted to result in the amino acid substitution p.Glu1447Ala. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0066% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/4-15597733-A-C). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
GeneDx RCV000594523 SCV005373289 likely pathogenic not provided 2024-04-03 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 protein structure/function; Has not been previously published as pathogenic or benign in association with neurodevelopmental disorders to our knowledge; This variant is associated with the following publications: (PMID: 31964843)
OMIM RCV000023923 SCV000045214 pathogenic Joubert syndrome 9/15, digenic 2012-01-15 no assertion criteria provided literature only

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