Variant chrX-18174117-T-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_153346.5(BEND2):c.1894A>T(p.Arg632Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,209,990 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R632K) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000089 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.0000018 ( 0 hom. 0 hem. )

Consequence

BEND2
NM_153346.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.367

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:

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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=0.07682145).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BEND2	NM_153346.5 linkuse as main transcript	c.1894A>T	p.Arg632Trp	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.1894A>T	p.Arg632Trp	missense_variant	12/14	1	NM_153346.5	P1	Q8NDZ0-1
BEND2	ENST00000380030.4 linkuse as main transcript	c.1621A>T	p.Arg541Trp	missense_variant	10/11	1			Q8NDZ0-2

Frequencies

GnomAD3 genomes

AF:

0.00000892

AC:

AN:

112170

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34300

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:

0.0000188

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000182

AC:

AN:

1097820

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

363196

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:

0.00000238

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000892

AC:

AN:

112170

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34300

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:

0.0000188

Gnomad4 OTH

AF:

0.00

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

Feb 12, 2024

The c.1894A>T (p.R632W) alteration is located in exon 12 (coding exon 12) of the BEND2 gene. This alteration results from a A to T substitution at nucleotide position 1894, causing the arginine (R) at amino acid position 632 to be replaced by a tryptophan (W). 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

-0.45

BayesDel_noAF

Benign

-0.88

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.0048

T;.

FATHMM_MKL

Benign

0.096

LIST_S2

Benign

0.57

T;T

M_CAP

Benign

0.0061

MetaRNN

Benign

0.077

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.0

N;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.22

PROVEAN

Benign

-0.87

N;N

REVEL

Benign

0.017

Sift4G

Uncertain

0.0040

D;D

Polyphen

0.059

B;.

Vest4

0.099

MutPred

0.24

Gain of ubiquitination at K631 (P = 0.0222);.;

MVP

0.030

MPC

0.31

ClinPred

0.092

GERP RS

1.9

Varity_R

0.15

gMVP

0.12

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