2-218960151-C-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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. 14/22 in silico tools predict 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. P111A) has been classified as Uncertain significance.

• 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
• Publications: 1 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: Benign. The variant received -8 ACMG points.

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

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.331C>T	p.Pro111Ser	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.331C>T	p.Pro111Ser	missense	Exon 1 of 1	ENSP00000304250.4	Q13319
	CDK5R2-AS1	ENST00000429343.1	TSL:4	n.45+1708G>A		intron	N/A
	CDK5R2-AS1	ENST00000798770.1		n.277+1708G>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000941 AC: 16 AN: 170114 AF XY: 0.0000938

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 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

African (AFR) AF: 0.0000336 AC: 1 AN: 29726

American (AMR) AF: 0.00 AC: 0 AN: 38540

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24916

East Asian (EAS) AF: 0.00 AC: 0 AN: 34398

South Asian (SAS) AF: 0.000483 AC: 39 AN: 80804

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47358

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5582

European-Non Finnish (NFE) AF: 0.00000275 AC: 3 AN: 1090852

Other (OTH) AF: 0.0000171 AC: 1 AN: 58394

GnomAD4 genome Cov.: 32

Alfa AF: 0.00109 Hom.: 0

Bravo AF: 0.0000113

ExAC AF: 0.000102 AC: 12

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		0.86
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
PromoterAI		-0.063	Neutral
Varity_R		0.039
gMVP		0.30
Mutation Taster		=97/3	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: rs770916373; hg19: chr2-219824873; COSMIC: COSV56937071;