chr8-22613025-A-C

Variant names:

• chr8-22613025-A-C
• rs200084191
• ENST00000520861.5:c.-383A>C

Variant summary

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

The ENST00000520861.5(CCAR2):​c.-383A>C variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,460,680 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: CCAR2 ENST00000520861.5 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.17
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.120324254).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000520861.5. 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
	CCAR2	NM_001393997.1	MANE Select	c.593A>C	p.Tyr198Ser	missense	Exon 8 of 21	NP_001380926.1	Q8N163-1
	CCAR2	NM_021174.6		c.593A>C	p.Tyr198Ser	missense	Exon 8 of 21	NP_066997.3
	CCAR2	NM_001363068.2		c.593A>C	p.Tyr198Ser	missense	Exon 8 of 21	NP_001349997.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCAR2	ENST00000520861.5	TSL:1	c.-383A>C		5_prime_UTR_premature_start_codon_gain	Exon 4 of 16	ENSP00000429773.1	G3V119
	CCAR2	ENST00000308511.9	TSL:1 MANE Select	c.593A>C	p.Tyr198Ser	missense	Exon 8 of 21	ENSP00000310670.4	Q8N163-1
	CCAR2	ENST00000389279.7	TSL:1	c.593A>C	p.Tyr198Ser	missense	Exon 8 of 21	ENSP00000373930.3	Q8N163-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1460680 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 726738

African (AFR) AF: 0.00 AC: 0 AN: 33420

American (AMR) AF: 0.00 AC: 0 AN: 44488

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26122

East Asian (EAS) AF: 0.00 AC: 0 AN: 39644

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86092

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53398

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5540

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111642

Other (OTH) AF: 0.00 AC: 0 AN: 60334

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.022	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	22
DANN	Benign	0.94
DEOGEN2	Benign	0.058	T
Eigen	Benign	0.017
Eigen_PC	Benign	0.20
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		3.2
PrimateAI	Uncertain	0.79	T
PROVEAN	Benign	0.11	N
REVEL	Benign	0.11
Sift	Benign	0.32	T
Sift4G	Benign	0.13	T
Polyphen		0.39	B
Vest4		0.53
MutPred		0.19		Loss of stability (P = 0.0251)
MVP		0.55
MPC		1.4
ClinPred		0.38	T
GERP RS		5.9
PromoterAI		-0.011	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.067
gMVP		0.42
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs200084191; hg19: chr8-22470538;