ClinVar Miner

Submissions for variant NM_017950.4(CCDC40):c.257A>G (p.Tyr86Cys)

gnomAD frequency: 0.00010  dbSNP: rs202220442
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV001094481 SCV000407163 uncertain significance Primary ciliary dyskinesia 15 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Invitae RCV000317319 SCV000933857 uncertain significance Primary ciliary dyskinesia 2024-01-15 criteria provided, single submitter clinical testing This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 86 of the CCDC40 protein (p.Tyr86Cys). This variant is present in population databases (rs202220442, gnomAD 0.01%). This missense change has been observed in individual(s) with heterotaxy syndrome (PMID: 34768622). ClinVar contains an entry for this variant (Variation ID: 325722). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests 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.
Ambry Genetics RCV000317319 SCV002739594 uncertain significance Primary ciliary dyskinesia 2017-02-07 criteria provided, single submitter clinical testing The p.Y86C variant (also known as c.257A>G), located in coding exon 3 of the CCDC40 gene, results from an A to G substitution at nucleotide position 257. The tyrosine at codon 86 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is poorly 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.

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