Variant X-103310427-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_032621.4(BEX2):c.-75G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,155,752 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 6 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 0.000035 ( 0 hom., 2 hem., cov: 23)

Exomes 𝑓: 0.0000086 ( 0 hom. 4 hem. )

Consequence

BEX2
NM_032621.4 5_prime_UTR

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0380

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 -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.09188634).

BS2

High Hemizygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
BEX2	NM_032621.4 linkuse as main transcript	c.-75G>C		5_prime_UTR_variant	2/3	ENST00000372677.8
BEX2	NM_001168399.2 linkuse as main transcript	c.22G>C	p.Gly8Arg	missense_variant	2/3
BEX2	NM_001168400.2 linkuse as main transcript	c.19G>C	p.Gly7Arg	missense_variant	2/3
BEX2	NM_001168401.2 linkuse as main transcript	c.-75G>C		5_prime_UTR_variant	2/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BEX2	ENST00000372677.8 linkuse as main transcript	c.-75G>C		5_prime_UTR_variant	2/3	1	NM_032621.4	P1	Q9BXY8-1
BEX2	ENST00000536889.1 linkuse as main transcript	c.22G>C	p.Gly8Arg	missense_variant	2/3	2			Q9BXY8-2
BEX2	ENST00000372674.5 linkuse as main transcript	c.-75G>C		5_prime_UTR_variant	2/3	2		P1	Q9BXY8-1
BEX2	ENST00000449185.1 linkuse as main transcript	c.-75G>C		5_prime_UTR_variant	2/3	3

Frequencies

GnomAD3 genomes

AF:

0.0000354

AC:

AN:

112854

Hom.:

Cov.:

AF XY:

0.0000571

AC XY:

AN XY:

35004

show subpopulations

Gnomad AFR

AF:

0.0000321

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000924

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:

0.00131

GnomAD3 exomes

AF:

0.0000194

AC:

AN:

103030

Hom.:

AF XY:

0.0000268

AC XY:

AN XY:

37244

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000103

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000863

AC:

AN:

1042898

Hom.:

Cov.:

AF XY:

0.0000117

AC XY:

AN XY:

341414

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000717

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000401

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000244

Gnomad4 OTH exome

AF:

0.0000678

GnomAD4 genome

AF:

0.0000354

AC:

AN:

112854

Hom.:

Cov.:

AF XY:

0.0000571

AC XY:

AN XY:

35004

show subpopulations

Gnomad4 AFR

AF:

0.0000321

Gnomad4 AMR

AF:

0.0000924

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:

0.00131

Bravo

AF:

0.0000680

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 13, 2023

The c.22G>C (p.G8R) alteration is located in exon 2 (coding exon 2) of the BEX2 gene. This alteration results from a G to C substitution at nucleotide position 22, causing the glycine (G) at amino acid position 8 to be replaced by an arginine (R). 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

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-1.0

CADD

Benign

5.3

DANN

Benign

0.86

FATHMM_MKL

Benign

0.017

LIST_S2

Benign

0.41

M_CAP

Benign

0.0077

MetaRNN

Benign

0.092

MetaSVM

Benign

-0.98

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.47

PROVEAN

Benign

-1.2

REVEL

Benign

0.017

Sift

Uncertain

0.028

Sift4G

Uncertain

0.051

Vest4

0.16

MutPred

0.45

Gain of sheet (P = 0.0221);

MVP

0.043

MPC

0.29

ClinPred

0.056

GERP RS

0.083

gMVP

0.012

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