Variant 8-22613126-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000308511.9(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
ENST00000308511.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.06

Variant links:

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]

CCAR2 links:

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ACMG classification

Classification made for transcript

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	Protein	UniProt
CCAR2	NM_001393997.1 linkuse as main transcript	c.694A>G	p.Thr232Ala	missense_variant	8/21	ENST00000308511.9	NP_001380926.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCAR2	ENST00000308511.9 linkuse as main transcript	c.694A>G	p.Thr232Ala	missense_variant	8/21	1	NM_001393997.1	ENSP00000310670	P1	Q8N163-1
CCAR2	ENST00000389279.7 linkuse as main transcript	c.694A>G	p.Thr232Ala	missense_variant	8/21	1		ENSP00000373930	P1	Q8N163-1
CCAR2	ENST00000520861.5 linkuse as main transcript	c.-282A>G		5_prime_UTR_variant	4/16	1		ENSP00000429773
CCAR2	ENST00000522599.5 linkuse as main transcript	c.148A>G	p.Thr50Ala	missense_variant	1/5	5		ENSP00000429739

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.90e-7

AC:

AN:

1449318

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

720964

show subpopulations

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.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 22, 2024

The c.694A>G (p.T232A) alteration is located in exon 8 (coding exon 7) of the CCAR2 gene. This alteration results from a A to G substitution at nucleotide position 694, causing the threonine (T) at amino acid position 232 to be replaced by an alanine (A). 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

Benign

0.060

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Benign

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

LIST_S2

Benign

0.58

.;T;T

M_CAP

Benign

0.0059

MetaRNN

Benign

0.069

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.34

N;N;.

MutationTaster

Benign

1.0

D;N;N

PrimateAI

Uncertain

0.58

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

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over