chr4-15601414-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_001378615.1(CC2D2A):c.4852C>T(p.Arg1618Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000567 in 1,482,572 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 Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1618G) has been classified as Uncertain significance.
Frequency
Consequence
NM_001378615.1 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CC2D2A | NM_001378615.1 | c.4852C>T | p.Arg1618Cys | missense_variant | 37/37 | ENST00000424120.6 | |
CC2D2A | NM_001080522.2 | c.4852C>T | p.Arg1618Cys | missense_variant | 38/38 | ||
CC2D2A | NM_001378617.1 | c.4705C>T | p.Arg1569Cys | missense_variant | 35/35 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CC2D2A | ENST00000424120.6 | c.4852C>T | p.Arg1618Cys | missense_variant | 37/37 | 5 | NM_001378615.1 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000223 AC: 34AN: 152150Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000694 AC: 11AN: 158472Hom.: 0 AF XY: 0.0000815 AC XY: 7AN XY: 85912
GnomAD4 exome AF: 0.0000368 AC: 49AN: 1330304Hom.: 0 Cov.: 31 AF XY: 0.0000384 AC XY: 25AN XY: 650746
GnomAD4 genome AF: 0.000230 AC: 35AN: 152268Hom.: 0 Cov.: 33 AF XY: 0.000215 AC XY: 16AN XY: 74440
ClinVar
Submissions by phenotype
Meckel-Gruber syndrome;C0431399:Familial aplasia of the vermis Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 01, 2022 | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 1618 of the CC2D2A protein (p.Arg1618Cys). This variant is present in population databases (rs201219078, gnomAD 0.05%). This variant has not been reported in the literature in individuals affected with CC2D2A-related conditions. ClinVar contains an entry for this variant (Variation ID: 238282). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt CC2D2A protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Joubert syndrome 9;C2676790:Meckel syndrome, type 6;C5435651:COACH syndrome 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 31, 2018 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jul 23, 2019 | In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge - |
Joubert syndrome 9 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Aug 03, 2019 | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at