Variant 11-34152499-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_145804.3(ABTB2):c.2966G>A(p.Arg989Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000225 in 1,609,818 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00019 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00023 ( 0 hom. )

Consequence

ABTB2
NM_145804.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.432

Variant links:

Genes affected

ABTB2 (HGNC:23842): (ankyrin repeat and BTB domain containing 2) Predicted to enable protein heterodimerization activity. Predicted to act upstream of or within cellular response to toxic substance. [provided by Alliance of Genome Resources, Apr 2022]

ABTB2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.059643954).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABTB2	NM_145804.3 linkuse as main transcript	c.2966G>A	p.Arg989Gln	missense_variant	17/17	ENST00000435224.3	NP_665803.2	Q8N961-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABTB2	ENST00000435224.3 linkuse as main transcript	c.2966G>A	p.Arg989Gln	missense_variant	17/17	1	NM_145804.3	ENSP00000410157.2		Q8N961-1

Frequencies

GnomAD3 genomes

AF:

0.000191

AC:

AN:

152136

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000523

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000250

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000310

AC:

AN:

241658

Hom.:

AF XY:

0.000222

AC XY:

AN XY:

130790

show subpopulations

Gnomad AFR exome

AF:

0.000128

Gnomad AMR exome

AF:

0.000800

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000502

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000305

Gnomad OTH exome

AF:

0.000676

GnomAD4 exome

AF:

0.000228

AC:

333

AN:

1457682

Hom.:

Cov.:

AF XY:

0.000210

AC XY:

152

AN XY:

724664

show subpopulations

Gnomad4 AFR exome

AF:

0.0000897

Gnomad4 AMR exome

AF:

0.000792

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000202

Gnomad4 SAS exome

AF:

0.0000117

Gnomad4 FIN exome

AF:

0.0000378

Gnomad4 NFE exome

AF:

0.000239

Gnomad4 OTH exome

AF:

0.000199

GnomAD4 genome

AF:

0.000191

AC:

AN:

152136

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74308

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.000523

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000250

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000302

Hom.:

Bravo

AF:

0.000280

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000582

AC:

ExAC

AF:

0.000272

AC:

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

Oct 26, 2021

The c.2966G>A (p.R989Q) alteration is located in exon 17 (coding exon 17) of the ABTB2 gene. This alteration results from a G to A substitution at nucleotide position 2966, causing the arginine (R) at amino acid position 989 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

Benign

0.13

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.32

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.041

Eigen

Benign

-0.0086

Eigen_PC

Benign

0.11

FATHMM_MKL

Benign

0.56

LIST_S2

Uncertain

0.97

M_CAP

Benign

0.038

MetaRNN

Benign

0.060

MetaSVM

Benign

-0.76

MutationAssessor

Benign

1.0

PrimateAI

Benign

0.43

PROVEAN

Benign

-1.4

REVEL

Benign

0.15

Sift

Uncertain

0.0050

Sift4G

Uncertain

0.013

Vest4

0.21

MVP

0.47

MPC

0.19

ClinPred

0.017

GERP RS

4.8

Varity_R

0.15

gMVP

0.47

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