chr4-15563422-CG-C
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_001378615.1(CC2D2A):βc.3084delβ(p.Lys1029ArgfsTer3) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000205 in 1,609,774 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (β β ). Synonymous variant affecting the same amino acid position (i.e. R1028R) 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.3084del | p.Lys1029ArgfsTer3 | frameshift_variant | 24/37 | ENST00000424120.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CC2D2A | ENST00000424120.6 | c.3084del | p.Lys1029ArgfsTer3 | frameshift_variant | 24/37 | 5 | NM_001378615.1 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152164Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000829 AC: 2AN: 241344Hom.: 1 AF XY: 0.00 AC XY: 0AN XY: 130704
GnomAD4 exome AF: 0.0000185 AC: 27AN: 1457610Hom.: 0 Cov.: 31 AF XY: 0.0000248 AC XY: 18AN XY: 724622
GnomAD4 genome AF: 0.0000394 AC: 6AN: 152164Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74330
ClinVar
Submissions by phenotype
not provided Pathogenic:3
Pathogenic, criteria provided, single submitter | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Jul 08, 2022 | PM2, PM3, PVS1 - |
Pathogenic, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Jul 07, 2022 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Dec 06, 2021 | Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 33543475, 29620724, 30202406, 19466712, 27894351, 21493627, 19777577, 31130284) - |
Meckel syndrome, type 6 Pathogenic:2
Likely pathogenic, no assertion criteria provided | literature only | Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM) | - | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Pathology and Clinical Laboratory Medicine, King Fahad Medical City | - | - - |
Meckel-Gruber syndrome;C0431399:Familial aplasia of the vermis Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Nov 21, 2023 | This sequence change creates a premature translational stop signal (p.Lys1029Argfs*3) 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). This variant is present in population databases (rs764571764, gnomAD 0.009%). This premature translational stop signal has been observed in individuals with Meckel syndrome (PMID: 19466712, 27894351). ClinVar contains an entry for this variant (Variation ID: 56301). For these reasons, this variant has been classified as Pathogenic. - |
Joubert syndrome 9 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center | Mar 26, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at