rs777203757
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_018249.6(CDK5RAP2):c.1340G>A(p.Arg447His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000143 in 1,611,100 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict 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. R447C) has been classified as Uncertain significance.
Frequency
Consequence
NM_018249.6 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CDK5RAP2 | NM_018249.6 | c.1340G>A | p.Arg447His | missense_variant | 13/38 | ENST00000349780.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDK5RAP2 | ENST00000349780.9 | c.1340G>A | p.Arg447His | missense_variant | 13/38 | 1 | NM_018249.6 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152058Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000240 AC: 6AN: 249584Hom.: 0 AF XY: 0.0000370 AC XY: 5AN XY: 135010
GnomAD4 exome AF: 0.0000137 AC: 20AN: 1459042Hom.: 0 Cov.: 29 AF XY: 0.0000138 AC XY: 10AN XY: 725992
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152058Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74280
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Oct 27, 2016 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Apr 18, 2022 | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 447 of the CDK5RAP2 protein (p.Arg447His). This variant is present in population databases (rs777203757, gnomAD 0.005%). This variant has not been reported in the literature in individuals affected with CDK5RAP2-related conditions. ClinVar contains an entry for this variant (Variation ID: 434648). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0". The histidine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at