rs780591693

Variant names:

• chr2-218960250-G-A
• rs780591693
• NM_003936.5:c.430G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-218960250-G-A
• chr2-218960250-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003936.5(CDK5R2):​c.430G>A​(p.Ala144Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000894 in 1,119,094 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 8.9e-7 (0 hom.)
• Consequence: CDK5R2 NM_003936.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.132

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08661106).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDK5R2	NM_003936.5	c.430G>A	p.Ala144Thr	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.430G>A	p.Ala144Thr	missense_variant	Exon 1 of 1	6	NM_003936.5	ENSP00000304250.4
CDK5R2-AS1	ENST00000429343.1	n.45+1609C>T		intron_variant	Intron 1 of 1	4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 8.94e-7 AC: 1 AN: 1119094 Hom.: 0 Cov.: 31 AF XY: 0.00000186 AC XY: 1 AN XY: 536588

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000106

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.056	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.35	T
M_CAP	Uncertain	0.28	D
MetaRNN	Benign	0.087	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.90	L
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	-0.23	N
REVEL	Benign	0.048
Sift	Benign	0.48	T
Sift4G	Benign	0.62	T
Polyphen		0.0010	B
Vest4		0.071
MutPred		0.35		Gain of glycosylation at A144 (P = 0.0122);
MVP		0.44
ClinPred		0.056	T
GERP RS		0.76
Varity_R		0.030
gMVP		0.24

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: rs780591693; hg19: chr2-219824972;