rs2289526
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_017950.4(CCDC40):c.142G>A(p.Gly48Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000372 in 1,613,750 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_017950.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CCDC40 | NM_017950.4 | c.142G>A | p.Gly48Ser | missense_variant | 3/20 | ENST00000397545.9 | |
CCDC40 | NM_001243342.2 | c.142G>A | p.Gly48Ser | missense_variant | 3/18 | ||
CCDC40 | NM_001330508.2 | c.142G>A | p.Gly48Ser | missense_variant | 3/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CCDC40 | ENST00000397545.9 | c.142G>A | p.Gly48Ser | missense_variant | 3/20 | 5 | NM_017950.4 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000132 AC: 2AN: 151904Hom.: 0 Cov.: 30
GnomAD3 exomes AF: 0.0000364 AC: 9AN: 247072Hom.: 0 AF XY: 0.0000447 AC XY: 6AN XY: 134274
GnomAD4 exome AF: 0.0000397 AC: 58AN: 1461846Hom.: 0 Cov.: 31 AF XY: 0.0000385 AC XY: 28AN XY: 727228
GnomAD4 genome ? AF: 0.0000132 AC: 2AN: 151904Hom.: 0 Cov.: 30 AF XY: 0.0000135 AC XY: 1AN XY: 74150
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 27, 2021 | This sequence change replaces glycine with serine at codon 48 of the CCDC40 protein (p.Gly48Ser). The glycine residue is moderately conserved and there is a small physicochemical difference between glycine and serine. This variant is present in population databases (rs2289526, ExAC 0.02%). This variant has not been reported in the literature in individuals affected with CCDC40-related conditions. ClinVar contains an entry for this variant (Variation ID: 454877). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The serine 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. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 13, 2024 | The p.G48S variant (also known as c.142G>A), located in coding exon 3 of the CCDC40 gene, results from a G to A substitution at nucleotide position 142. The glycine at codon 48 is replaced by serine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this alteration remains unclear. - |
Primary ciliary dyskinesia 15 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at