Variant X-18174125-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_153346.5(BEND2):c.1886G>C(p.Arg629Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000967 in 1,209,973 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 33 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., 2 hem., cov: 22)

Exomes 𝑓: 0.000094 ( 0 hom. 31 hem. )

Consequence

BEND2
NM_153346.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.274

Variant links:

Genes affected

BEND2 (HGNC:28509): (BEN domain containing 2) This gene encodes a protein which has two BEN domains in the C-terminus. These domains are found in proteins which participate in protein and DNA interactions which occur during chromatin restructuring or transcription. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2011]

BEND2 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=0.077156514).

BS2

High Hemizygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BEND2	NM_153346.5 linkuse as main transcript	c.1886G>C	p.Arg629Thr	missense_variant	12/14	ENST00000380033.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BEND2	ENST00000380033.9 linkuse as main transcript	c.1886G>C	p.Arg629Thr	missense_variant	12/14	1	NM_153346.5	P1	Q8NDZ0-1
BEND2	ENST00000380030.4 linkuse as main transcript	c.1613G>C	p.Arg538Thr	missense_variant	10/11	1			Q8NDZ0-2

Frequencies

GnomAD3 genomes

AF:

0.000125

AC:

AN:

112123

Hom.:

Cov.:

AF XY:

0.0000583

AC XY:

AN XY:

34287

show subpopulations

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:

0.000263

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000273

AC:

AN:

183256

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

67778

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.0000612

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000938

AC:

103

AN:

1097850

Hom.:

Cov.:

AF XY:

0.0000853

AC XY:

AN XY:

363234

show subpopulations

Gnomad4 AFR exome

AF:

0.0000379

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:

0.000113

Gnomad4 OTH exome

AF:

0.000152

GnomAD4 genome

AF:

0.000125

AC:

AN:

112123

Hom.:

Cov.:

AF XY:

0.0000583

AC XY:

AN XY:

34287

show subpopulations

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:

0.000263

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.0000869

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000692

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000297

AC:

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.000218

EpiControl

AF:

0.000119

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

May 17, 2023

The c.1886G>C (p.R629T) alteration is located in exon 12 (coding exon 12) of the BEND2 gene. This alteration results from a G to C substitution at nucleotide position 1886, causing the arginine (R) at amino acid position 629 to be replaced by a threonine (T). 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

0.16

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.78

CADD

Benign

DANN

Benign

0.90

DEOGEN2

Benign

0.011

T;.

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.55

T;T

M_CAP

Benign

0.0046

MetaRNN

Benign

0.077

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

L;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.24

PROVEAN

Benign

-1.6

N;N

REVEL

Benign

0.028

Sift4G

Uncertain

0.0020

D;D

Polyphen

0.65

P;.

Vest4

0.17

MVP

0.030

MPC

0.37

ClinPred

0.036

GERP RS

1.5

Varity_R

0.29

gMVP

0.17

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