dbSNP rs144468375: CDK2AP2:p.Gln60Gln (chr11-67507592-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 2P and 12B. PP3_ModerateBP6_Very_StrongBS2

The NM_005851.5(CDK2AP2):c.180G>A(p.Gln60Gln) variant causes a splice region, synonymous change. The variant allele was found at a frequency of 0.012 in 1,613,638 control chromosomes in the GnomAD database, including 142 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0088 ( 5 hom., cov: 33)

Exomes 𝑓: 0.012 ( 137 hom. )

Consequence

CDK2AP2
NM_005851.5 splice_region, synonymous

Scores

Splicing: ADA: 0.9998

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 4.72

Publications

3 publications found

Variant links:

Genes affected

CDK2AP2 (HGNC:30833): (cyclin dependent kinase 2 associated protein 2) This gene encodes a protein that interacts with cyclin-dependent kinase 2 associated protein 1. Pseudogenes associated with this gene are located on chromosomes 7 and 9. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, Dec 2012]

CDK2AP2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

PP3

Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF. No scorers claiming Uncertain. Scorers claiming Benign: max_spliceai.

BP6

Variant 11-67507592-C-T is Benign according to our data. Variant chr11-67507592-C-T is described in ClinVar as Benign. ClinVar VariationId is 770402.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005851.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CDK2AP2	NM_005851.5	MANE Select	c.180G>A	p.Gln60Gln	splice_region synonymous	Exon 2 of 4	NP_005842.1	O75956
CDK2AP2	NM_001271849.2		c.15G>A	p.Gln5Gln	splice_region synonymous	Exon 2 of 4	NP_001258778.1
CDK2AP2	NR_073484.2		n.571G>A		splice_region non_coding_transcript_exon	Exon 1 of 3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CDK2AP2	ENST00000301488.8	TSL:1 MANE Select	c.180G>A	p.Gln60Gln	splice_region synonymous	Exon 2 of 4	ENSP00000301488.4	O75956
CDK2AP2	ENST00000531178.1	TSL:1	n.*135G>A		splice_region non_coding_transcript_exon	Exon 2 of 4	ENSP00000436213.1	E9PQJ3
CDK2AP2	ENST00000531178.1	TSL:1	n.*135G>A		3_prime_UTR	Exon 2 of 4	ENSP00000436213.1	E9PQJ3

Frequencies

GnomAD3 genomes

AF:

0.00881

AC:

1342

AN:

152264

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00200

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.00687

Gnomad ASJ

AF:

0.0164

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.00536

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0148

Gnomad OTH

AF:

0.0100

GnomAD2 exomes

AF:

0.00911

AC:

2282

AN:

250498

AF XY:

0.00886

show subpopulations

Gnomad AFR exome

AF:

0.00315

Gnomad AMR exome

AF:

0.00668

Gnomad ASJ exome

AF:

0.0181

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00703

Gnomad NFE exome

AF:

0.0138

Gnomad OTH exome

AF:

0.00916

GnomAD4 exome

AF:

0.0124

AC:

18091

AN:

1461256

Hom.:

137

Cov.:

AF XY:

0.0121

AC XY:

8790

AN XY:

726916

show subpopulations

African (AFR)

AF:

0.00251

AC:

AN:

33478

American (AMR)

AF:

0.00657

AC:

294

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.0167

AC:

436

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.00192

AC:

166

AN:

86254

European-Finnish (FIN)

AF:

0.00772

AC:

408

AN:

52844

Middle Eastern (MID)

AF:

0.0144

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0144

AC:

16015

AN:

1111974

Other (OTH)

AF:

0.0100

AC:

604

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

1049

2098

3146

4195

5244

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

608

1216

1824

2432

3040

<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:

0.00881

AC:

1342

AN:

152382

Hom.:

Cov.:

AF XY:

0.00840

AC XY:

626

AN XY:

74522

show subpopulations

African (AFR)

AF:

0.00200

AC:

AN:

41592

American (AMR)

AF:

0.00686

AC:

105

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.0164

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.00124

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00536

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0148

AC:

1008

AN:

68032

Other (OTH)

AF:

0.00993

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

159

239

318

398

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.0121

Hom.:

Bravo

AF:

0.00886

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.0153

EpiControl

AF:

0.0158

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.42

CADD

Benign

(source)

DANN

Benign

0.95

PhyloP100

4.7

PromoterAI

0.14

Neutral

(source)

Mutation Taster

=25/75

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.98

SpliceAI score (max)

0.020

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over