rs771732758
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Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 10P and 2B. PVS1PM2BP6_Moderate
The NM_017950.4(CCDC40):c.29+1_29+13dup variant causes a stop gained, frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000105 in 1,462,272 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.00053 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000056 ( 0 hom. )
Consequence
CCDC40
NM_017950.4 stop_gained, frameshift
NM_017950.4 stop_gained, frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.0240
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_pathogenic. Variant got 8 ACMG points.
PVS1
?
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 47 pathogenic variants in the truncated region.
PM2
?
Very rare variant in population databases, with high coverage;
BP6
?
Variant 17-80036684-G-GCGGGCCGGTAAGC is Benign according to our data. Variant chr17-80036684-G-GCGGGCCGGTAAGC is described in ClinVar as [Likely_benign]. Clinvar id is 454886.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CCDC40 | NM_017950.4 | c.29+1_29+13dup | stop_gained, frameshift_variant | 1/20 | ENST00000397545.9 | ||
CCDC40 | NM_001243342.2 | c.29+1_29+13dup | stop_gained, frameshift_variant | 1/18 | |||
CCDC40 | NM_001330508.2 | c.29+1_29+13dup | stop_gained, frameshift_variant | 1/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CCDC40 | ENST00000397545.9 | c.29+1_29+13dup | stop_gained, frameshift_variant | 1/20 | 5 | NM_017950.4 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.000533 AC: 81AN: 152058Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000308 AC: 3AN: 97410Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 55550
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GnomAD4 exome AF: 0.0000557 AC: 73AN: 1310102Hom.: 0 Cov.: 31 AF XY: 0.0000404 AC XY: 26AN XY: 644020
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GnomAD4 genome ? AF: 0.000526 AC: 80AN: 152170Hom.: 0 Cov.: 32 AF XY: 0.000457 AC XY: 34AN XY: 74390
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Primary ciliary dyskinesia Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 05, 2023 | - - |
Computational scores
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at