ClinVar Miner

Submissions for variant NM_017721.5(CC2D1A):c.2657G>A (p.Arg886His)

gnomAD frequency: 0.00072  dbSNP: rs201921029
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV000502989 SCV000593883 uncertain significance not specified 2016-09-14 criteria provided, single submitter clinical testing
Invitae RCV000892683 SCV001036576 uncertain significance not provided 2022-06-23 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 886 of the CC2D1A protein (p.Arg886His). This variant is present in population databases (rs201921029, gnomAD 0.1%), and has an allele count higher than expected for a pathogenic variant. This missense change has been observed in individual(s) with clinical features CC2D1A-related conditions (PMID: 27799067). ClinVar contains an entry for this variant (Variation ID: 254203). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The histidine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.
CeGaT Center for Human Genetics Tuebingen RCV000892683 SCV001249846 uncertain significance not provided 2019-08-01 criteria provided, single submitter clinical testing
Ambry Genetics RCV001267084 SCV001445265 uncertain significance Inborn genetic diseases 2019-07-12 criteria provided, single submitter clinical testing The p.R886H variant (also known as c.2657G>A), located in coding exon 26 of the CC2D1A gene, results from a G to A substitution at nucleotide position 2657. The arginine at codon 886 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Baylor Genetics RCV001333956 SCV001526675 uncertain significance Intellectual disability, autosomal recessive 3 2018-07-11 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
GeneDx RCV000892683 SCV001989074 uncertain significance not provided 2022-09-29 criteria provided, single submitter clinical testing Observed with an additional missense variant in a patient with developmental delay, behavior problems, and dysmorphic features in published literature, but it is not known whether the variants occurred on the same (in cis) or on different (in trans) chromosomes (Loviglio et al., 2016); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 27799067)
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine RCV000491719 SCV000299210 pathogenic Smith-Magenis Syndrome-like 2016-08-15 flagged submission research

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