rs2069398

chr12-55967092-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_001798.5(CDK2):c.84G>A(p.Glu28=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0862 in 1,613,304 control chromosomes in the GnomAD database, including 7,962 homozygotes. 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: 𝑓 0.13 (2043 hom., cov: 32)
  • Exomes 𝑓: 0.082 (5919 hom.)
• Consequence: CDK2 NM_001798.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.890

Genes affected

CDK2 (HGNC:1771): (cyclin dependent kinase 2) This gene encodes a member of a family of serine/threonine protein kinases that participate in cell cycle regulation. The encoded protein is the catalytic subunit of the cyclin-dependent protein kinase complex, which regulates progression through the cell cycle. Activity of this protein is especially critical during the G1 to S phase transition. This protein associates with and regulated by other subunits of the complex including cyclin A or E, CDK inhibitor p21Cip1 (CDKN1A), and p27Kip1 (CDKN1B). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2014]

(HGNC:):

PMEL (HGNC:10880): (premelanosome protein) This gene encodes a melanocyte-specific type I transmembrane glycoprotein. The encoded protein is enriched in melanosomes, which are the melanin-producing organelles in melanocytes, and plays an essential role in the structural organization of premelanosomes. This protein is involved in generating internal matrix fibers that define the transition from Stage I to Stage II melanosomes. This protein undergoes a complex pattern of prosttranslational processing and modification that is essential to the proper functioning of the protein. A secreted form of this protein that is released by proteolytic ectodomain shedding may be used as a melanoma-specific serum marker. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jan 2011]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.3).
• BP7: Synonymous conserved (PhyloP=0.89 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.279 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDK2	NM_001798.5	c.84G>A	p.Glu28=	synonymous_variant	1/7	ENST00000266970.9
CDK2	NM_052827.4	c.84G>A	p.Glu28=	synonymous_variant	1/6
CDK2	NM_001290230.2	c.84G>A	p.Glu28=	synonymous_variant	1/5
CDK2	XM_011537732.2	c.84G>A	p.Glu28=	synonymous_variant	1/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDK2	ENST00000266970.9	c.84G>A	p.Glu28=	synonymous_variant	1/7	1	NM_001798.5	P1
	ENST00000554022.1	n.311C>T		non_coding_transcript_exon_variant	2/2	4

Frequencies

GnomAD3 genomes AF: 0.130 AC: 19854 AN: 152170 Hom.: 2011 Cov.: 32

Gnomad AFR AF: 0.282

Gnomad AMI AF: 0.0965

Gnomad AMR AF: 0.0758

Gnomad ASJ AF: 0.0856

Gnomad EAS AF: 0.00635

Gnomad SAS AF: 0.0557

Gnomad FIN AF: 0.0689

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0784

Gnomad OTH AF: 0.105

GnomAD3 exomes AF: 0.0796 AC: 19725 AN: 247936 Hom.: 1243 AF XY: 0.0754 AC XY: 10124 AN XY: 134184

Gnomad AFR exome AF: 0.295

Gnomad AMR exome AF: 0.0575

Gnomad ASJ exome AF: 0.0809

Gnomad EAS exome AF: 0.00561

Gnomad SAS exome AF: 0.0538

Gnomad FIN exome AF: 0.0722

Gnomad NFE exome AF: 0.0763

Gnomad OTH exome AF: 0.0743

GnomAD4 exome AF: 0.0816 AC: 119203 AN: 1461016 Hom.: 5919 Cov.: 31 AF XY: 0.0797 AC XY: 57944 AN XY: 726736

Gnomad4 AFR exome AF: 0.296

Gnomad4 AMR exome AF: 0.0621

Gnomad4 ASJ exome AF: 0.0802

Gnomad4 EAS exome AF: 0.00446

Gnomad4 SAS exome AF: 0.0542

Gnomad4 FIN exome AF: 0.0734

Gnomad4 NFE exome AF: 0.0809

Gnomad4 OTH exome AF: 0.0887

GnomAD4 genome AF: 0.131 AC: 19944 AN: 152288 Hom.: 2043 Cov.: 32 AF XY: 0.128 AC XY: 9541 AN XY: 74474

Gnomad4 AFR AF: 0.283

Gnomad4 AMR AF: 0.0757

Gnomad4 ASJ AF: 0.0856

Gnomad4 EAS AF: 0.00636

Gnomad4 SAS AF: 0.0558

Gnomad4 FIN AF: 0.0689

Gnomad4 NFE AF: 0.0784

Gnomad4 OTH AF: 0.108

Alfa AF: 0.0969 Hom.: 748

Bravo AF: 0.138

Asia WGS AF: 0.0750 AC: 260 AN: 3478

EpiCase AF: 0.0774

EpiControl AF: 0.0767

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
Cadd	Benign	15
Dann	Benign	0.95

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: rs2069398; hg19: chr12-56360876; COSMIC: COSV57186031; COSMIC: COSV57186031;