rs863225171
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_001378615.1(CC2D2A):c.3744_3747dup(p.Pro1250GlyfsTer11) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000709 in 1,551,270 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★★). Synonymous variant affecting the same amino acid position (i.e. L1248L) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_001378615.1 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CC2D2A | NM_001378615.1 | c.3744_3747dup | p.Pro1250GlyfsTer11 | frameshift_variant | 29/37 | ENST00000424120.6 | |
CC2D2A | NM_001080522.2 | c.3744_3747dup | p.Pro1250GlyfsTer11 | frameshift_variant | 30/38 | ||
CC2D2A | NM_001378617.1 | c.3597_3600dup | p.Pro1201GlyfsTer11 | frameshift_variant | 27/35 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CC2D2A | ENST00000424120.6 | c.3744_3747dup | p.Pro1250GlyfsTer11 | frameshift_variant | 29/37 | 5 | NM_001378615.1 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152204Hom.: 0 Cov.: 33
GnomAD4 exome AF: 0.00000643 AC: 9AN: 1399066Hom.: 0 Cov.: 31 AF XY: 0.00000290 AC XY: 2AN XY: 690058
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152204Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74376
ClinVar
Submissions by phenotype
Meckel-Gruber syndrome;C0431399:Familial aplasia of the vermis Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Sep 26, 2021 | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 217599). This premature translational stop signal has been observed in individual(s) with Joubert syndrome (PMID: 26092869). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Pro1250Glyfs*11) in the CC2D2A gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CC2D2A are known to be pathogenic (PMID: 19777577). - |
Joubert syndrome 9 Pathogenic:1
Pathogenic, criteria provided, single submitter | research | UW Hindbrain Malformation Research Program, University of Washington | Feb 23, 2015 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at