rs1345420961

Variant names:

• chr2-218960185-C-A
• rs1345420961
• 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. The variant received 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A122V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CDK5R2 NM_003936.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.78
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3455134).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003936.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDK5R2	NM_003936.5	MANE Select	c.365C>A	p.Ala122Glu	missense	Exon 1 of 1	NP_003927.1	Q13319

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDK5R2	ENST00000302625.6	TSL:6 MANE Select	c.365C>A	p.Ala122Glu	missense	Exon 1 of 1	ENSP00000304250.4	Q13319
	CDK5R2-AS1	ENST00000429343.1	TSL:4	n.45+1674G>T		intron	N/A
	CDK5R2-AS1	ENST00000798770.1		n.277+1674G>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		3.8
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
Mutation Taster		=86/14	polymorphism

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

Other links and lift over

dbSNP: rs1345420961; hg19: chr2-219824907; COSMIC: COSV56935693;