rs148403620
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBS1_Supporting
The NM_018249.6(CDK5RAP2):āc.3686A>Gā(p.Asn1229Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000341 in 1,614,146 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 (ā ā ).
Frequency
Consequence
NM_018249.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CDK5RAP2 | NM_018249.6 | c.3686A>G | p.Asn1229Ser | missense_variant | 24/38 | ENST00000349780.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDK5RAP2 | ENST00000349780.9 | c.3686A>G | p.Asn1229Ser | missense_variant | 24/38 | 1 | NM_018249.6 | P4 |
Frequencies
GnomAD3 genomes AF: 0.000217 AC: 33AN: 152184Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000519 AC: 13AN: 250530Hom.: 0 AF XY: 0.0000443 AC XY: 6AN XY: 135472
GnomAD4 exome AF: 0.0000150 AC: 22AN: 1461844Hom.: 0 Cov.: 33 AF XY: 0.0000124 AC XY: 9AN XY: 727222
GnomAD4 genome AF: 0.000217 AC: 33AN: 152302Hom.: 0 Cov.: 32 AF XY: 0.000201 AC XY: 15AN XY: 74460
ClinVar
Submissions by phenotype
Microcephaly 3, primary, autosomal recessive Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Feb 08, 2013 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 03, 2023 | This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 1229 of the CDK5RAP2 protein (p.Asn1229Ser). This variant is present in population databases (rs148403620, gnomAD 0.05%). 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: 158144). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Not Available". The serine 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