Variant chrX-103309596-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_032621.4(BEX2):c.381G>T(p.Met127Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000911 in 1,097,269 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0 ( 0 hom., 0 hem., cov: 20)

Exomes 𝑓: 0.0000091 ( 0 hom. 2 hem. )

Failed GnomAD Quality Control

Consequence

BEX2
NM_032621.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.70

Variant links:

Genes affected

BEX2 (HGNC:30933): (brain expressed X-linked 2) This gene belongs to the brain expressed X-linked gene family. The encoded protein interacts with the transcription factor LIM domain only 2 in a DNA-binding complex that recognizes the E-box element and promotes transcription. This gene has been found to be a tumor suppressor that is silenced in human glioma. In breast cancer cells, this gene product modulates apoptosis in response to estrogen and tamoxifen, and enhances the anti-proliferative effect of tamoxifen. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2009]

BEX2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.2938869).

BS2

High Hemizygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
BEX2	NM_032621.4 linkuse as main transcript	c.381G>T	p.Met127Ile	missense_variant	3/3	ENST00000372677.8
BEX2	NM_001168399.2 linkuse as main transcript	c.477G>T	p.Met159Ile	missense_variant	3/3
BEX2	NM_001168400.2 linkuse as main transcript	c.474G>T	p.Met158Ile	missense_variant	3/3
BEX2	NM_001168401.2 linkuse as main transcript	c.381G>T	p.Met127Ile	missense_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BEX2	ENST00000372677.8 linkuse as main transcript	c.381G>T	p.Met127Ile	missense_variant	3/3	1	NM_032621.4	P1	Q9BXY8-1
BEX2	ENST00000536889.1 linkuse as main transcript	c.477G>T	p.Met159Ile	missense_variant	3/3	2			Q9BXY8-2
BEX2	ENST00000372674.5 linkuse as main transcript	c.381G>T	p.Met127Ile	missense_variant	3/3	2		P1	Q9BXY8-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

110297

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

32503

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000911

AC:

AN:

1097269

Hom.:

Cov.:

AF XY:

0.00000551

AC XY:

AN XY:

362731

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:

0.0000119

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

110297

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

32503

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

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

Dec 14, 2023

The c.477G>T (p.M159I) alteration is located in exon 3 (coding exon 3) of the BEX2 gene. This alteration results from a G to T substitution at nucleotide position 477, causing the methionine (M) at amino acid position 159 to be replaced by an isoleucine (I). 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

0.87

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.048

T;.;T

FATHMM_MKL

Benign

0.53

M_CAP

Uncertain

0.13

MetaRNN

Benign

0.29

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.7

M;.;M

MutationTaster

Benign

0.90

N;N;N

PrimateAI

Uncertain

0.63

PROVEAN

Benign

-1.4

N;N;N

REVEL

Benign

0.21

Sift

Benign

0.20

T;T;T

Sift4G

Benign

0.31

T;T;T

Polyphen

0.96

D;.;D

Vest4

0.33

MutPred

0.55

Loss of loop (P = 0.2237);.;Loss of loop (P = 0.2237);

MVP

0.20

MPC

0.31

ClinPred

0.88

GERP RS

2.5

Varity_R

0.36

gMVP

0.014

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