Variant chrX-18171168-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_153346.5(BEND2):c.2018C>T(p.Pro673Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 0.0000037 ( 0 hom. 3 hem. )

Failed GnomAD Quality Control

Consequence

BEND2
NM_153346.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.44

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BEND2	NM_153346.5 linkuse as main transcript	c.2018C>T	p.Pro673Leu	missense_variant	13/14	ENST00000380033.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BEND2	ENST00000380033.9 linkuse as main transcript	c.2018C>T	p.Pro673Leu	missense_variant	13/14	1	NM_153346.5	P1	Q8NDZ0-1
BEND2	ENST00000380030.4 linkuse as main transcript	c.1745C>T	p.Pro582Leu	missense_variant	11/11	1			Q8NDZ0-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000109

AC:

AN:

182947

Hom.:

AF XY:

0.00

AC XY:

AN XY:

67587

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:

0.0000245

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000365

AC:

AN:

1095428

Hom.:

Cov.:

AF XY:

0.00000831

AC XY:

AN XY:

361036

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:

0.00000476

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000165

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

Sep 15, 2021

The c.2018C>T (p.P673L) alteration is located in exon 13 (coding exon 13) of the BEND2 gene. This alteration results from a C to T substitution at nucleotide position 2018, causing the proline (P) at amino acid position 673 to be replaced by a leucine (L). 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

Uncertain

0.47

BayesDel_addAF

Benign

-0.066

BayesDel_noAF

Benign

-0.28

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.12

T;.

FATHMM_MKL

Benign

0.40

LIST_S2

Benign

0.55

T;T

M_CAP

Benign

0.027

MetaRNN

Uncertain

0.55

D;D

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.2

L;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.39

PROVEAN

Uncertain

-3.5

D;D

REVEL

Benign

0.27

Sift4G

Uncertain

0.0020

D;D

Polyphen

0.96

D;.

Vest4

0.69

MutPred

0.58

Gain of helix (P = 0.0022);.;

MVP

0.12

MPC

0.54

ClinPred

0.84

GERP RS

4.6

Varity_R

0.48

gMVP

0.73

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