4-121823883-C-T

Variant names:

• chr4-121823883-C-T
• rs769236
• NM_001237.5:c.-255G>A

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4 BA1

The NM_001237.5(CCNA2):​c.-255G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.359 in 557,246 control chromosomes in the GnomAD database, including 39,192 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 0.30 (8351 hom., cov: 34)
  • Exomes 𝑓: 0.38 (30841 hom.)
• Consequence: CCNA2 NM_001237.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.47
• Publications: 15 publications found

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

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.13).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.424 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCNA2	NM_001237.5	c.-255G>A		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	c.-255G>A		5_prime_UTR_variant	Exon 1 of 8	1	NM_001237.5	ENSP00000274026.5

Frequencies

GnomAD3 genomes AF: 0.300 AC: 45619 AN: 152116 Hom.: 8344 Cov.: 34

Gnomad AFR AF: 0.0779

Gnomad AMI AF: 0.401

Gnomad AMR AF: 0.405

Gnomad ASJ AF: 0.355

Gnomad EAS AF: 0.439

Gnomad SAS AF: 0.338

Gnomad FIN AF: 0.404

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.378

Gnomad OTH AF: 0.303

GnomAD4 exome AF: 0.381 AC: 154373 AN: 405012 Hom.: 30841 Cov.: 5 AF XY: 0.379 AC XY: 79689 AN XY: 210456

African (AFR) AF: 0.0759 AC: 635 AN: 8362

American (AMR) AF: 0.448 AC: 5092 AN: 11362

Ashkenazi Jewish (ASJ) AF: 0.342 AC: 4009 AN: 11734

East Asian (EAS) AF: 0.526 AC: 13086 AN: 24886

South Asian (SAS) AF: 0.331 AC: 10572 AN: 31912

European-Finnish (FIN) AF: 0.428 AC: 11902 AN: 27800

Middle Eastern (MID) AF: 0.351 AC: 636 AN: 1814

European-Non Finnish (NFE) AF: 0.379 AC: 99912 AN: 263730

Other (OTH) AF: 0.364 AC: 8529 AN: 23412

GnomAD4 genome AF: 0.300 AC: 45634 AN: 152234 Hom.: 8351 Cov.: 34 AF XY: 0.304 AC XY: 22637 AN XY: 74414

African (AFR) AF: 0.0778 AC: 3233 AN: 41570

American (AMR) AF: 0.406 AC: 6205 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.355 AC: 1231 AN: 3468

East Asian (EAS) AF: 0.439 AC: 2269 AN: 5172

South Asian (SAS) AF: 0.339 AC: 1637 AN: 4828

European-Finnish (FIN) AF: 0.404 AC: 4273 AN: 10580

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.378 AC: 25683 AN: 67996

Other (OTH) AF: 0.304 AC: 643 AN: 2116

Alfa AF: 0.198 Hom.: 481

Bravo AF: 0.290

Asia WGS AF: 0.363 AC: 1266 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.13
CADD	Benign	19
DANN	Uncertain	0.98
PhyloP100		1.5
PromoterAI		-0.063	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Mutation Taster		=239/61	polymorphism (auto)

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

Other links and lift over

dbSNP: rs769236; hg19: chr4-122745038;