chr8-22613126-A-G

Position:

• chr8-22613126-A-G

Variant summary

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

The NM_001393997.1(CCAR2):​c.694A>G​(p.Thr232Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000069 in 1,449,318 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: CCAR2 NM_001393997.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.06

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=0.06852031).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCAR2	NM_001393997.1	c.694A>G	p.Thr232Ala	missense_variant	8/21	ENST00000308511.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCAR2	ENST00000308511.9	c.694A>G	p.Thr232Ala	missense_variant	8/21	1	NM_001393997.1	P1
CCAR2	ENST00000389279.7	c.694A>G	p.Thr232Ala	missense_variant	8/21	1		P1
CCAR2	ENST00000520861.5	c.-282A>G		5_prime_UTR_variant	4/16	1
CCAR2	ENST00000522599.5	c.148A>G	p.Thr50Ala	missense_variant	1/5	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.90e-7 AC: 1 AN: 1449318 Hom.: 0 Cov.: 30 AF XY: 0.00000139 AC XY: 1 AN XY: 720964

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.060
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	13
DANN	Uncertain	0.98
DEOGEN2	Benign	0.067	T;T;T
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.38
FATHMM_MKL	Benign	0.49	N
M_CAP	Benign	0.0059	T
MetaRNN	Benign	0.069	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.34	N;N;.
MutationTaster	Benign	1.0	D;N;N
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	0.16	N;N;N
REVEL	Benign	0.024
Sift	Benign	0.51	T;T;T
Sift4G	Uncertain	0.037	D;D;D
Polyphen		0.0	B;B;.
Vest4		0.36
MutPred		0.26		Loss of glycosylation at T232 (P = 0.0618);Loss of glycosylation at T232 (P = 0.0618);.;
MVP		0.25
MPC		0.12
ClinPred		0.071	T
GERP RS		2.0
Varity_R		0.020
gMVP		0.30

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: rs1008664503; hg19: chr8-22470639;