rs761870224

Variant names:

• chr4-121818161-C-A
• rs761870224
• NM_001237.5:c.1133G>T

Your query was ambiguous. Multiple possible variants found:

• chr4-121818161-C-A
• chr4-121818161-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001237.5(CCNA2):​c.1133G>T​(p.Arg378Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R378Q) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CCNA2 NM_001237.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.61
• Publications: 0 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.111501426).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCNA2	NM_001237.5	MANE Select	c.1133G>T	p.Arg378Leu	missense	Exon 7 of 8	NP_001228.2	P20248

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCNA2	ENST00000274026.10	TSL:1 MANE Select	c.1133G>T	p.Arg378Leu	missense	Exon 7 of 8	ENSP00000274026.5	P20248
	CCNA2	ENST00000876644.1		c.1148G>T	p.Arg383Leu	missense	Exon 7 of 8	ENSP00000546703.1
	CCNA2	ENST00000940444.1		c.1139G>T	p.Arg380Leu	missense	Exon 7 of 8	ENSP00000610503.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	15
DANN	Benign	0.85
DEOGEN2	Benign	0.17	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.64	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.11	N
PhyloP100		1.6
PrimateAI	Benign	0.19	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.053
Sift	Benign	0.33	T
Sift4G	Benign	0.31	T
Polyphen		0.0	B
Vest4		0.12
MutPred		0.57		Gain of glycosylation at Y382 (P = 0.0429)
MVP		0.24
MPC		0.84
ClinPred		0.14	T
GERP RS		-4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.40
gMVP		0.15
Mutation Taster		=83/17	polymorphism

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: rs761870224; hg19: chr4-122739316;