chr8-22607297-C-G

Position:

• chr8-22607297-C-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.459C>G​(p.His153Gln) 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. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CCAR2 NM_001393997.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.444

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=0.1567241).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCAR2	NM_001393997.1	c.459C>G	p.His153Gln	missense_variant	6/21	ENST00000308511.9	NP_001380926.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCAR2	ENST00000308511.9	c.459C>G	p.His153Gln	missense_variant	6/21	1	NM_001393997.1	ENSP00000310670.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 04, 2024

The c.459C>G (p.H153Q) alteration is located in exon 6 (coding exon 5) of the CCAR2 gene. This alteration results from a C to G substitution at nucleotide position 459, causing the histidine (H) at amino acid position 153 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.70
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.093	T;T;.
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.22
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.80	.;T;T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.16	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.26	N;N;.
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-0.59	N;N;N
REVEL	Benign	0.13
Sift	Benign	0.23	T;T;D
Sift4G	Benign	0.20	T;T;T
Polyphen		0.38	B;B;.
Vest4		0.30
MutPred		0.21		Loss of helix (P = 0.0041);Loss of helix (P = 0.0041);Loss of helix (P = 0.0041);
MVP		0.37
MPC		2.1
ClinPred		0.71	D
GERP RS		0.26
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.042
gMVP		0.59

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: rs1801113194; hg19: chr8-22464810;