rs375586063
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Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The NM_017950.4(CCDC40):āc.384A>Gā(p.Ala128=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000133 in 1,614,062 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: š 0.00022 ( 0 hom., cov: 32)
Exomes š: 0.00012 ( 0 hom. )
Consequence
CCDC40
NM_017950.4 synonymous
NM_017950.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.44
Genes affected
CCDC40 (HGNC:26090): (coiled-coil domain 40 molecular ruler complex subunit) This gene encodes a protein that is necessary for motile cilia function. It functions in correct left-right axis formation by regulating the assembly of the inner dynein arm and the dynein regulatory complexes, which control ciliary beat. Mutations in this gene cause ciliary dyskinesia type 15, a disorder due to defects in cilia motility. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2011]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.98).
BP6
?
Variant 17-80040102-A-G is Benign according to our data. Variant chr17-80040102-A-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 260973.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=3, Uncertain_significance=1}.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CCDC40 | NM_017950.4 | c.384A>G | p.Ala128= | synonymous_variant | 3/20 | ENST00000397545.9 | |
CCDC40 | NM_001243342.2 | c.384A>G | p.Ala128= | synonymous_variant | 3/18 | ||
CCDC40 | NM_001330508.2 | c.384A>G | p.Ala128= | synonymous_variant | 3/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CCDC40 | ENST00000397545.9 | c.384A>G | p.Ala128= | synonymous_variant | 3/20 | 5 | NM_017950.4 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.000217 AC: 33AN: 152198Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000161 AC: 40AN: 249110Hom.: 0 AF XY: 0.000133 AC XY: 18AN XY: 135252
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GnomAD4 exome AF: 0.000124 AC: 182AN: 1461864Hom.: 0 Cov.: 33 AF XY: 0.000133 AC XY: 97AN XY: 727236
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GnomAD4 genome ? AF: 0.000217 AC: 33AN: 152198Hom.: 0 Cov.: 32 AF XY: 0.000202 AC XY: 15AN XY: 74364
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:3
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Primary ciliary dyskinesia Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 08, 2017 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 19, 2023 | - - |
Primary ciliary dyskinesia 15 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at