rs3217772

Variant names:

• chr4-121818028-C-G
• rs3217772
• NM_001237.5:c.1250+16G>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+16G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.375 in 1,601,058 control chromosomes in the GnomAD database, including 117,956 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 (8375 hom., cov: 32)
  • Exomes 𝑓: 0.38 (109581 hom.)
• Consequence: CCNA2 NM_001237.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.53
• Publications: 12 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=-0.76).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.426 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCNA2	NM_001237.5	MANE Select	c.1250+16G>C		intron	N/A	NP_001228.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCNA2	ENST00000274026.10	TSL:1 MANE Select	c.1250+16G>C		intron	N/A	ENSP00000274026.5

Frequencies

GnomAD3 genomes AF: 0.300 AC: 45663 AN: 152000 Hom.: 8368 Cov.: 32

Gnomad AFR AF: 0.0779

Gnomad AMI AF: 0.402

Gnomad AMR AF: 0.407

Gnomad ASJ AF: 0.355

Gnomad EAS AF: 0.442

Gnomad SAS AF: 0.339

Gnomad FIN AF: 0.404

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.378

Gnomad OTH AF: 0.305

GnomAD2 exomes AF: 0.373 AC: 90890 AN: 243978 AF XY: 0.371

Gnomad AFR exome AF: 0.0678

Gnomad AMR exome AF: 0.510

Gnomad ASJ exome AF: 0.350

Gnomad EAS exome AF: 0.418

Gnomad FIN exome AF: 0.410

Gnomad NFE exome AF: 0.377

Gnomad OTH exome AF: 0.391

GnomAD4 exome AF: 0.383 AC: 554952 AN: 1448940 Hom.: 109581 Cov.: 30 AF XY: 0.380 AC XY: 274093 AN XY: 721072

African (AFR) AF: 0.0636 AC: 2098 AN: 33012

American (AMR) AF: 0.493 AC: 21118 AN: 42814

Ashkenazi Jewish (ASJ) AF: 0.341 AC: 8771 AN: 25706

East Asian (EAS) AF: 0.491 AC: 19462 AN: 39642

South Asian (SAS) AF: 0.323 AC: 27410 AN: 84754

European-Finnish (FIN) AF: 0.421 AC: 22417 AN: 53194

Middle Eastern (MID) AF: 0.344 AC: 1969 AN: 5720

European-Non Finnish (NFE) AF: 0.389 AC: 429650 AN: 1104234

Other (OTH) AF: 0.368 AC: 22057 AN: 59864

GnomAD4 genome AF: 0.300 AC: 45677 AN: 152118 Hom.: 8375 Cov.: 32 AF XY: 0.305 AC XY: 22652 AN XY: 74356

African (AFR) AF: 0.0778 AC: 3229 AN: 41514

American (AMR) AF: 0.407 AC: 6231 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.355 AC: 1232 AN: 3466

East Asian (EAS) AF: 0.441 AC: 2280 AN: 5170

South Asian (SAS) AF: 0.340 AC: 1639 AN: 4822

European-Finnish (FIN) AF: 0.404 AC: 4261 AN: 10550

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

European-Non Finnish (NFE) AF: 0.378 AC: 25697 AN: 67976

Other (OTH) AF: 0.306 AC: 648 AN: 2116

Alfa AF: 0.333 Hom.: 1677

Bravo AF: 0.291

Asia WGS AF: 0.364 AC: 1268 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	2.6
DANN	Benign	0.71
PhyloP100		-1.5
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: rs3217772; hg19: chr4-122739183; COSMIC: COSV54665302; COSMIC: COSV54665302;