2-218960151-C-T

Variant names:

• chr2-218960151-C-T
• rs770916373
• NM_003936.5:c.331C>T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_003936.5(CDK5R2):​c.331C>T​(p.Pro111Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000312 in 1,410,570 control chromosomes in the GnomAD database, including 2 homozygotes. 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: 0.000031 (2 hom.)
• Consequence: CDK5R2 NM_003936.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.864

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 Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.050858557).
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDK5R2	NM_003936.5	c.331C>T	p.Pro111Ser	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.331C>T	p.Pro111Ser	missense_variant	Exon 1 of 1	6	NM_003936.5	ENSP00000304250.4
CDK5R2-AS1	ENST00000429343.1	n.45+1708G>A		intron_variant	Intron 1 of 1	4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000941 AC: 16 AN: 170114 Hom.: 0 AF XY: 0.0000938 AC XY: 9 AN XY: 95956

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000653

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000312 AC: 44 AN: 1410570 Hom.: 2 Cov.: 32 AF XY: 0.0000414 AC XY: 29 AN XY: 700236

Gnomad4 AFR exome AF: 0.0000336

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000483

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000275

Gnomad4 OTH exome AF: 0.0000171

GnomAD4 genome Cov.: 32

Alfa AF: 0.000136 Hom.: 0

Bravo AF: 0.0000113

ExAC AF: 0.000102 AC: 12

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.063
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.060	T
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.42
FATHMM_MKL	Benign	0.54	D
LIST_S2	Benign	0.52	T
M_CAP	Pathogenic	0.36	D
MetaRNN	Benign	0.051	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.11	N
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	0.43	N
REVEL	Benign	0.054
Sift	Benign	0.52	T
Sift4G	Benign	0.61	T
Polyphen		0.032	B
Vest4		0.086
MutPred		0.35		Loss of catalytic residue at P111 (P = 7e-04);
MVP		0.55
ClinPred		0.033	T
GERP RS		3.5
Varity_R		0.039
gMVP		0.30

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: rs770916373; hg19: chr2-219824873; COSMIC: COSV56937071;