rs981570225

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr2-218960265-G-A
• chr2-218960265-G-C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_003936.5(CDK5R2):​c.445G>A​(p.Gly149Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000118 in 1,275,692 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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. G149V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000071 (0 hom.)
• Consequence: CDK5R2 NM_003936.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.40
• 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.09455472).

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.445G>A	p.Gly149Ser	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.445G>A	p.Gly149Ser	missense	Exon 1 of 1	ENSP00000304250.4	Q13319
	CDK5R2-AS1	ENST00000429343.1	TSL:4	n.45+1594C>T		intron	N/A
	CDK5R2-AS1	ENST00000798770.1		n.277+1594C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000463 AC: 7 AN: 151042 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000461

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000711 AC: 8 AN: 1124542 Hom.: 0 Cov.: 31 AF XY: 0.00000556 AC XY: 3 AN XY: 539698

African (AFR) AF: 0.00 AC: 0 AN: 22664

American (AMR) AF: 0.000361 AC: 3 AN: 8306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14402

East Asian (EAS) AF: 0.00 AC: 0 AN: 25870

South Asian (SAS) AF: 0.00 AC: 0 AN: 28868

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 24916

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3106

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 951186

Other (OTH) AF: 0.000111 AC: 5 AN: 45224

GnomAD4 genome AF: 0.0000463 AC: 7 AN: 151150 Hom.: 0 Cov.: 32 AF XY: 0.0000542 AC XY: 4 AN XY: 73836

African (AFR) AF: 0.00 AC: 0 AN: 41394

American (AMR) AF: 0.000461 AC: 7 AN: 15200

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3452

East Asian (EAS) AF: 0.00 AC: 0 AN: 5090

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10196

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67698

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000147

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.047	T
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.48
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.56	T
M_CAP	Pathogenic	0.40	D
MetaRNN	Benign	0.095	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.0	L
PhyloP100		1.4
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	0.45	N
REVEL	Benign	0.11
Sift	Benign	0.67	T
Sift4G	Benign	1.0	T
Polyphen		0.11	B
Vest4		0.12
MutPred		0.35		Gain of glycosylation at G149 (P = 0.0047)
MVP		0.60
ClinPred		0.20	T
GERP RS		3.8
Varity_R		0.17
gMVP		0.22
Mutation Taster		=94/6	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: rs981570225; hg19: chr2-219824987;