rs1392635342
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001378615.1(CC2D2A):c.585_586dup(p.Thr196IlefsTer63) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000069 in 1,449,510 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 6.9e-7 ( 0 hom. )
Consequence
CC2D2A
NM_001378615.1 frameshift
NM_001378615.1 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.0280
Genes affected
CC2D2A (HGNC:29253): (coiled-coil and C2 domain containing 2A) This gene encodes a coiled-coil and calcium binding domain protein that appears to play a critical role in cilia formation. Mutations in this gene cause Meckel syndrome type 6, as well as Joubert syndrome type 9. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2009]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 4-15511290-T-TTA is Pathogenic according to our data. Variant chr4-15511290-T-TTA is described in ClinVar as [Likely_pathogenic]. Clinvar id is 547169.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CC2D2A | NM_001378615.1 | c.585_586dup | p.Thr196IlefsTer63 | frameshift_variant | 8/37 | ENST00000424120.6 | |
LOC124900672 | XR_007058062.1 | n.252+3165_252+3166insTA | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CC2D2A | ENST00000424120.6 | c.585_586dup | p.Thr196IlefsTer63 | frameshift_variant | 8/37 | 5 | NM_001378615.1 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
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33
GnomAD3 exomes AF: 0.00000430 AC: 1AN: 232520Hom.: 0 AF XY: 0.00000792 AC XY: 1AN XY: 126250
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GnomAD4 exome AF: 6.90e-7 AC: 1AN: 1449510Hom.: 0 Cov.: 30 AF XY: 0.00000139 AC XY: 1AN XY: 720384
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GnomAD4 genome ? Cov.: 33
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ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Joubert syndrome 9 Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Centre for Translational Omics - GOSgene, University College London | Mar 16, 2018 | - - |
Computational scores
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at