dbSNP rs3217773: CCNA2:c.1250+78T>C (chr4-121817966-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001237.5(CCNA2):c.1250+78T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.307 in 1,396,368 control chromosomes in the GnomAD database, including 67,861 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 0.27 ( 6221 hom., cov: 32)

Exomes 𝑓: 0.31 ( 61640 hom. )

Consequence

CCNA2
NM_001237.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.335

Publications

9 publications found

Variant links:

Genes affected

CCNA2 (HGNC:1578): (cyclin A2) The protein encoded by this gene belongs to the highly conserved cyclin family, whose members function as regulators of the cell cycle. This protein binds and activates cyclin-dependent kinase 2 and thus promotes transition through G1/S and G2/M. [provided by RefSeq, Aug 2016]

CCNA2 Gene-Disease associations (from GenCC):

neurodevelopmental disorder
Inheritance: AR Classification: LIMITED Submitted by: G2P

CCNA2 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_001237.5, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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=-0.87).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.319 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001237.5. 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
	CCNA2	NM_001237.5	MANE Select	c.1250+78T>C		intron	N/A	NP_001228.2	P20248

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CCNA2	ENST00000274026.10	TSL:1 MANE Select	c.1250+78T>C	intron	N/A	ENSP00000274026.5	P20248
CCNA2	ENST00000876644.1		c.1265+78T>C	intron	N/A	ENSP00000546703.1
CCNA2	ENST00000940444.1		c.1256+78T>C	intron	N/A	ENSP00000610503.1

Frequencies

GnomAD3 genomes

AF:

0.271

AC:

41220

AN:

152068

Hom.:

6218

Cov.:

show subpopulations

Gnomad AFR

AF:

0.149

Gnomad AMI

AF:

0.227

Gnomad AMR

AF:

0.304

Gnomad ASJ

AF:

0.316

Gnomad EAS

AF:

0.197

Gnomad SAS

AF:

0.304

Gnomad FIN

AF:

0.379

Gnomad MID

AF:

0.297

Gnomad NFE

AF:

0.323

Gnomad OTH

AF:

0.276

GnomAD4 exome

AF:

0.311

AC:

387336

AN:

1244182

Hom.:

61640

AF XY:

0.313

AC XY:

195467

AN XY:

624034

show subpopulations

African (AFR)

AF:

0.139

AC:

3987

AN:

28688

American (AMR)

AF:

0.315

AC:

11437

AN:

36278

Ashkenazi Jewish (ASJ)

AF:

0.322

AC:

6885

AN:

21362

East Asian (EAS)

AF:

0.186

AC:

7171

AN:

38620

South Asian (SAS)

AF:

0.323

AC:

23576

AN:

73008

European-Finnish (FIN)

AF:

0.363

AC:

16929

AN:

46644

Middle Eastern (MID)

AF:

0.277

AC:

1286

AN:

4644

European-Non Finnish (NFE)

AF:

0.319

AC:

300683

AN:

942362

Other (OTH)

AF:

0.293

AC:

15382

AN:

52576

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

12836

25672

38507

51343

64179

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9188

18376

27564

36752

45940

<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:

0.271

AC:

41234

AN:

152186

Hom.:

6221

Cov.:

AF XY:

0.274

AC XY:

20419

AN XY:

74398

show subpopulations

African (AFR)

AF:

0.149

AC:

6189

AN:

41532

American (AMR)

AF:

0.304

AC:

4653

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.316

AC:

1095

AN:

3470

East Asian (EAS)

AF:

0.197

AC:

1020

AN:

5172

South Asian (SAS)

AF:

0.303

AC:

1461

AN:

4822

European-Finnish (FIN)

AF:

0.379

AC:

4011

AN:

10594

Middle Eastern (MID)

AF:

0.289

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.323

AC:

21928

AN:

67984

Other (OTH)

AF:

0.277

AC:

585

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1473

2946

4420

5893

7366

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

432

864

1296

1728

2160

<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:

0.302

Hom.:

1223

Bravo

AF:

0.257

Asia WGS

AF:

0.230

AC:

798

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

4.7

(source)

DANN

Benign

0.73

PhyloP100

-0.34

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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