dbSNP rs2069414: CDK2:c.*290C>A (chr12-55971915-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001798.5(CDK2):c.*290C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0473 in 345,882 control chromosomes in the GnomAD database, including 504 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 0.041 ( 185 hom., cov: 32)

Exomes 𝑓: 0.053 ( 319 hom. )

Consequence

CDK2
NM_001798.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.85

Publications

11 publications found

Variant links:

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]

CDK2 links:

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]

PMEL links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.063 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
CDK2	NM_001798.5 link	c.*290C>A	3_prime_UTR_variant	Exon 7 of 7	ENST00000266970.9	NP_001789.2
CDK2	NM_052827.4 link	c.*290C>A	3_prime_UTR_variant	Exon 6 of 6		NP_439892.2
CDK2	NM_001290230.2 link	c.*290C>A	3_prime_UTR_variant	Exon 5 of 5		NP_001277159.1
CDK2	XM_011537732.2 link	c.*290C>A	3_prime_UTR_variant	Exon 8 of 8		XP_011536034.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDK2	ENST00000266970.9 link	c.*290C>A		3_prime_UTR_variant	Exon 7 of 7	1	NM_001798.5	ENSP00000266970.4

Frequencies

GnomAD3 genomes

AF:

0.0406

AC:

6168

AN:

152088

Hom.:

185

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0113

Gnomad AMI

AF:

0.0614

Gnomad AMR

AF:

0.0285

Gnomad ASJ

AF:

0.0135

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.0350

Gnomad FIN

AF:

0.0488

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0646

Gnomad OTH

AF:

0.0374

GnomAD4 exome

AF:

0.0526

AC:

10195

AN:

193676

Hom.:

319

Cov.:

AF XY:

0.0526

AC XY:

5235

AN XY:

99556

show subpopulations

African (AFR)

AF:

0.0156

AC:

AN:

5390

American (AMR)

AF:

0.0251

AC:

186

AN:

7422

Ashkenazi Jewish (ASJ)

AF:

0.0168

AC:

116

AN:

6890

East Asian (EAS)

AF:

0.000143

AC:

AN:

14010

South Asian (SAS)

AF:

0.0371

AC:

432

AN:

11636

European-Finnish (FIN)

AF:

0.0550

AC:

697

AN:

12676

Middle Eastern (MID)

AF:

0.0387

AC:

AN:

982

European-Non Finnish (NFE)

AF:

0.0660

AC:

8062

AN:

122124

Other (OTH)

AF:

0.0461

AC:

578

AN:

12546

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

450

901

1351

1802

2252

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

102

136

170

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0405

AC:

6170

AN:

152206

Hom.:

185

Cov.:

AF XY:

0.0396

AC XY:

2945

AN XY:

74408

show subpopulations

African (AFR)

AF:

0.0112

AC:

467

AN:

41536

American (AMR)

AF:

0.0285

AC:

435

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.0135

AC:

AN:

3470

East Asian (EAS)

AF:

0.000579

AC:

AN:

5182

South Asian (SAS)

AF:

0.0353

AC:

170

AN:

4822

European-Finnish (FIN)

AF:

0.0488

AC:

517

AN:

10598

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0646

AC:

4392

AN:

67996

Other (OTH)

AF:

0.0374

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

306

613

919

1226

1532

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

156

234

312

390

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0516

Hom.:

512

Bravo

AF:

0.0377

Asia WGS

AF:

0.0200

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.20

(source)

DANN

Benign

0.64

PhyloP100

-1.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over