Genetic Variant CCNA2:c.-255G>T (chr4-121823883-C-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001237.5(CCNA2):c.-255G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000739 in 405,704 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 34)

Exomes 𝑓: 0.0000074 ( 0 hom. )

Consequence

CCNA2
NM_001237.5 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.47

Publications

15 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.13).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCNA2	NM_001237.5 link	c.-255G>T		5_prime_UTR_variant	Exon 1 of 8	ENST00000274026.10	NP_001228.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCNA2	ENST00000274026.10 link	c.-255G>T		5_prime_UTR_variant	Exon 1 of 8	1	NM_001237.5	ENSP00000274026.5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000739

AC:

AN:

405704

Hom.:

Cov.:

AF XY:

0.00000949

AC XY:

AN XY:

210822

show subpopulations

African (AFR)

AF:

0.000120

AC:

AN:

8362

American (AMR)

AF:

0.00

AC:

AN:

11378

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

11750

East Asian (EAS)

AF:

0.00

AC:

AN:

24920

South Asian (SAS)

AF:

0.00

AC:

AN:

31992

European-Finnish (FIN)

AF:

0.00

AC:

AN:

27828

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1816

European-Non Finnish (NFE)

AF:

0.00000757

AC:

AN:

264210

Other (OTH)

AF:

0.00

AC:

AN:

23448

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Cov.:

Alfa

AF:

0.00

Hom.:

481

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.13

CADD

Benign

(source)

DANN

Uncertain

0.97

PhyloP100

1.5

PromoterAI

-0.082

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over