Genetic Variant CDK2AP2:p.Gln60Gln (chr11-67507592-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_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

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP6

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

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDK2AP2	NM_005851.5 link	c.180G>A	p.Gln60Gln	splice_region_variant, synonymous_variant	Exon 2 of 4	ENST00000301488.8	NP_005842.1	O75956Q6IAV4
CDK2AP2	NM_001271849.2 link	c.15G>A	p.Gln5Gln	splice_region_variant, synonymous_variant	Exon 2 of 4		NP_001258778.1
CDK2AP2	NR_073484.2 link	n.571G>A		splice_region_variant, non_coding_transcript_exon_variant	Exon 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDK2AP2	ENST00000301488.8 link	c.180G>A	p.Gln60Gln	splice_region_variant, synonymous_variant	Exon 2 of 4	1	NM_005851.5	ENSP00000301488.4		O75956

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

GnomAD3 exomes

AF:

0.00911

AC:

2282

AN:

250498

Hom.:

AF XY:

0.00886

AC XY:

1203

AN XY:

135734

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 SAS exome

AF:

0.00186

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

Gnomad4 AFR exome

AF:

0.00251

Gnomad4 AMR exome

AF:

0.00657

Gnomad4 ASJ exome

AF:

0.0167

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00192

Gnomad4 FIN exome

AF:

0.00772

Gnomad4 NFE exome

AF:

0.0144

Gnomad4 OTH exome

AF:

0.0100

GnomAD4 genome

AF:

0.00881

AC:

1342

AN:

152382

Hom.:

Cov.:

AF XY:

0.00840

AC XY:

626

AN XY:

74522

show subpopulations

Gnomad4 AFR

AF:

0.00200

Gnomad4 AMR

AF:

0.00686

Gnomad4 ASJ

AF:

0.0164

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.00536

Gnomad4 NFE

AF:

0.0148

Gnomad4 OTH

AF:

0.00993

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

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 31, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Benign

0.95

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over