rs1345420961

Variant names:

• chr2-218960185-C-A
• NM_003936.5:c.365C>A

Your query was ambiguous. Multiple possible variants found:

• chr2-218960185-C-A
• chr2-218960185-C-T

Variant summary

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

The NM_003936.5(CDK5R2):​c.365C>A​(p.Ala122Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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: 3.78

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=0.3455134).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDK5R2	NM_003936.5	c.365C>A	p.Ala122Glu	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.365C>A	p.Ala122Glu	missense_variant	Exon 1 of 1	6	NM_003936.5	ENSP00000304250.4
CDK5R2-AS1	ENST00000429343.1	n.45+1674G>T		intron_variant	Intron 1 of 1	4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.85
BayesDel_addAF	Benign	-0.059	T
BayesDel_noAF	Benign	-0.32
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.15	T
Eigen	Benign	-0.013
Eigen_PC	Benign	0.091
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.51	T
M_CAP	Pathogenic	0.88	D
MetaRNN	Benign	0.35	T
MetaSVM	Benign	-0.71	T
MutationAssessor	Benign	0.34	N
PrimateAI	Pathogenic	0.93	D
PROVEAN	Benign	-0.92	N
REVEL	Benign	0.24
Sift	Benign	0.21	T
Sift4G	Benign	0.92	T
Polyphen		0.55	P
Vest4		0.13
MutPred		0.32		Gain of solvent accessibility (P = 0.08);
MVP		0.75
ClinPred		0.56	D
GERP RS		4.1
Varity_R		0.38
gMVP		0.49

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-219824907; COSMIC: COSV56935693;