4-121817966-A-G

Variant names:

• chr4-121817966-A-G
• rs3217773
• NM_001237.5:c.1250+78T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.335
• Publications: 9 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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCNA2	NM_001237.5	c.1250+78T>C		intron_variant	Intron 7 of 7	ENST00000274026.10	NP_001228.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCNA2	ENST00000274026.10	c.1250+78T>C		intron_variant	Intron 7 of 7	1	NM_001237.5	ENSP00000274026.5

Frequencies

GnomAD3 genomes AF: 0.271 AC: 41220 AN: 152068 Hom.: 6218 Cov.: 32

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

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

GnomAD4 genome AF: 0.271 AC: 41234 AN: 152186 Hom.: 6221 Cov.: 32 AF XY: 0.274 AC XY: 20419 AN XY: 74398

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: 85 AN: 294

European-Non Finnish (NFE) AF: 0.323 AC: 21928 AN: 67984

Other (OTH) AF: 0.277 AC: 585 AN: 2114

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.7
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)

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: rs3217773; hg19: chr4-122739121;