rs769236

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr4-121823883-C-A
• chr4-121823883-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

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
• 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: 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	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	c.-255G>T		5_prime_UTR_variant	Exon 1 of 8	1	NM_001237.5	ENSP00000274026.5

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000739 AC: 3 AN: 405704 Hom.: 0 Cov.: 5 AF XY: 0.00000949 AC XY: 2 AN XY: 210822

African (AFR) AF: 0.000120 AC: 1 AN: 8362

American (AMR) AF: 0.00 AC: 0 AN: 11378

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11750

East Asian (EAS) AF: 0.00 AC: 0 AN: 24920

South Asian (SAS) AF: 0.00 AC: 0 AN: 31992

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 27828

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1816

European-Non Finnish (NFE) AF: 0.00000757 AC: 2 AN: 264210

Other (OTH) AF: 0.00 AC: 0 AN: 23448

GnomAD4 genome Cov.: 34

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	19
DANN	Uncertain	0.97
PhyloP100		1.5
PromoterAI		-0.082	Neutral
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

Other links and lift over

dbSNP: rs769236; hg19: chr4-122745038;