8-22608031-C-G

Variant names:

• chr8-22608031-C-G
• rs376168583
• NM_001393997.1:c.550C>G

Variant summary

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

The NM_001393997.1(CCAR2):​c.550C>G​(p.Arg184Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,690 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R184W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CCAR2 NM_001393997.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.71
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001393997.1. 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
	CCAR2	NM_001393997.1	MANE Select	c.550C>G	p.Arg184Gly	missense	Exon 7 of 21	NP_001380926.1	Q8N163-1
	CCAR2	NM_021174.6		c.550C>G	p.Arg184Gly	missense	Exon 7 of 21	NP_066997.3
	CCAR2	NM_001363068.2		c.550C>G	p.Arg184Gly	missense	Exon 7 of 21	NP_001349997.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCAR2	ENST00000308511.9	TSL:1 MANE Select	c.550C>G	p.Arg184Gly	missense	Exon 7 of 21	ENSP00000310670.4	Q8N163-1
	CCAR2	ENST00000389279.7	TSL:1	c.550C>G	p.Arg184Gly	missense	Exon 7 of 21	ENSP00000373930.3	Q8N163-1
	CCAR2	ENST00000520861.5	TSL:1	c.-426C>G		5_prime_UTR	Exon 3 of 16	ENSP00000429773.1	G3V119

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461690 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727118

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53292

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111966

Other (OTH) AF: 0.00 AC: 0 AN: 60386

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.53
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.41	T
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.067	D
MetaRNN	Uncertain	0.66	D
MetaSVM	Benign	-0.82	T
MutationAssessor	Benign	0.90	L
PhyloP100		2.7
PrimateAI	Uncertain	0.73	T
PROVEAN	Uncertain	-2.5	N
REVEL	Benign	0.26
Sift	Uncertain	0.013	D
Sift4G	Uncertain	0.014	D
Polyphen		0.99	D
Vest4		0.58
MutPred		0.49		Gain of relative solvent accessibility (P = 0.005)
MVP		0.59
MPC		2.4
ClinPred		0.92	D
GERP RS		4.9
Varity_R		0.30
gMVP		0.64
Mutation Taster		=84/16	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: rs376168583; hg19: chr8-22465544;