chr2-218960265-G-C

Variant names:

• chr2-218960265-G-C
• rs981570225
• NM_003936.5:c.445G>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_003936.5(CDK5R2):​c.445G>C​(p.Gly149Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CDK5R2 NM_003936.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.40

Genes affected

CDK5R2 (HGNC:1776): (cyclin dependent kinase 5 regulatory subunit 2) The protein encoded by this gene is a neuron-specific activator of CDK5 kinase. It associates with CDK5 to form an active kinase. This protein and neuron-specific CDK5 activator CDK5R1/p39NCK5A both share limited similarity to cyclins, and thus may define a distinct family of cyclin-dependent kinase activating proteins. [provided by RefSeq, Jul 2008]

CDK5R2-AS1 (HGNC:55677): (CDK5R2 antisense RNA 1)

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.33033413).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDK5R2	NM_003936.5	c.445G>C	p.Gly149Arg	missense_variant	Exon 1 of 1	ENST00000302625.6	NP_003927.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDK5R2	ENST00000302625.6	c.445G>C	p.Gly149Arg	missense_variant	Exon 1 of 1	6	NM_003936.5	ENSP00000304250.4
CDK5R2-AS1	ENST00000429343.1	n.45+1594C>G		intron_variant	Intron 1 of 1	4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Benign	-0.040	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.021
Eigen_PC	Benign	-0.053
FATHMM_MKL	Benign	0.59	D
LIST_S2	Benign	0.58	T
M_CAP	Pathogenic	0.81	D
MetaRNN	Benign	0.33	T
MetaSVM	Benign	-0.66	T
MutationAssessor	Benign	0.23	N
PrimateAI	Pathogenic	0.93	D
PROVEAN	Benign	-0.74	N
REVEL	Benign	0.25
Sift	Benign	0.13	T
Sift4G	Benign	0.31	T
Polyphen		0.96	D
Vest4		0.061
MutPred		0.45		Gain of methylation at G149 (P = 0.029);
MVP		0.73
ClinPred		0.53	D
GERP RS		3.8
Varity_R		0.24
gMVP		0.29

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs981570225; hg19: chr2-219824987;