2-218960150-T-C

Variant names:

• chr2-218960150-T-C
• rs1370035953
• NM_003936.5:c.330T>C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_003936.5(CDK5R2):​c.330T>C​(p.Asp110Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000709 in 1,410,476 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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: 7.1e-7 (0 hom.)
• Consequence: CDK5R2 NM_003936.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00100
• 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 -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP7: Synonymous conserved (PhyloP=0.001 with no splicing effect.

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.330T>C	p.Asp110Asp	synonymous	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.330T>C	p.Asp110Asp	synonymous	Exon 1 of 1	ENSP00000304250.4	Q13319
	CDK5R2-AS1	ENST00000429343.1	TSL:4	n.45+1709A>G		intron	N/A
	CDK5R2-AS1	ENST00000798770.1		n.277+1709A>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.09e-7 AC: 1 AN: 1410476 Hom.: 0 Cov.: 32 AF XY: 0.00000143 AC XY: 1 AN XY: 700166

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 29724

American (AMR) AF: 0.0000260 AC: 1 AN: 38402

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24924

East Asian (EAS) AF: 0.00 AC: 0 AN: 34344

South Asian (SAS) AF: 0.00 AC: 0 AN: 80830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47156

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5510

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1091176

Other (OTH) AF: 0.00 AC: 0 AN: 58410

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	7.9
DANN	Benign	0.71
PhyloP100		0.0010
PromoterAI		0.015	Neutral
Mutation Taster		=100/0	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: rs1370035953; hg19: chr2-219824872;