NM_001393997.1:c.640G>A

Variant names:

• chr8-22613072-G-A
• rs138079032
• NM_001393997.1:c.640G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001393997.1(CCAR2):​c.640G>A​(p.Ala214Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,460,502 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: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CCAR2 NM_001393997.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.24

Genes affected

CCAR2 (HGNC:23360): (cell cycle and apoptosis regulator 2) Enables RNA polymerase II complex binding activity and enzyme inhibitor activity. Involved in several processes, including regulation of cellular protein metabolic process; regulation of signal transduction; and regulation of transcription, DNA-templated. Located in several cellular components, including mitochondrial matrix; nucleoplasm; and spindle. Part of DBIRD complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1820125).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCAR2	NM_001393997.1	c.640G>A	p.Ala214Thr	missense_variant	Exon 8 of 21	ENST00000308511.9	NP_001380926.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCAR2	ENST00000308511.9	c.640G>A	p.Ala214Thr	missense_variant	Exon 8 of 21	1	NM_001393997.1	ENSP00000310670.4
CCAR2	ENST00000389279.7	c.640G>A	p.Ala214Thr	missense_variant	Exon 8 of 21	1		ENSP00000373930.3
CCAR2	ENST00000520861	c.-336G>A		5_prime_UTR_variant	Exon 4 of 16	1		ENSP00000429773.1
CCAR2	ENST00000522599.5	c.94G>A	p.Ala32Thr	missense_variant	Exon 1 of 5	5		ENSP00000429739.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000399 AC: 1 AN: 250638 Hom.: 0 AF XY: 0.00000738 AC XY: 1 AN XY: 135568

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000546

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460502 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 726640

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.34
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T;T;T
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.88	.;D;D
M_CAP	Benign	0.0067	T
MetaRNN	Benign	0.18	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.34	N;N;.
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-0.35	N;N;N
REVEL	Benign	0.16
Sift	Benign	0.071	T;T;T
Sift4G	Benign	0.14	T;T;T
Polyphen		0.99	D;D;.
Vest4		0.41
MutPred		0.28		Gain of glycosylation at A214 (P = 0.003);Gain of glycosylation at A214 (P = 0.003);.;
MVP		0.25
MPC		0.19
ClinPred		0.42	T
GERP RS		5.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.056
gMVP		0.25

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

Publications

LitVar

Other links and lift over

dbSNP: rs138079032; hg19: chr8-22470585;