rs782616912

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_001388464.1(H2BW2):c.257T>C(p.Ile86Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00045 in 1,192,847 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 207 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00046 ( 0 hom., 19 hem., cov: 24)

Exomes 𝑓: 0.00045 ( 0 hom. 188 hem. )

Consequence

H2BW2
NM_001388464.1 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:3

Conservation

PhyloP100: 6.67

Publications

0 publications found

Variant links:

Genes affected

H2BW2 (HGNC:27867): (H2B.W histone 2) Histones are basic nuclear proteins that are responsible for the nucleosome structure of the chromosomal fiber in eukaryotes. Two molecules of each of the four core histones (H2A, H2B, H3, and H4) form an octamer, around which approximately 146 bp of DNA is wrapped in repeating units, called nucleosomes. The linker histone, H1, interacts with linker DNA between nucleosomes and functions in the compaction of chromatin into higher order structures. This gene encodes a replication-independent histone that is a member of the H2B histone family. [provided by RefSeq, Nov 2015]

H2BW2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0672524).

BP6

Variant X-104040251-T-C is Benign according to our data. Variant chrX-104040251-T-C is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 522987.

BS2

High Hemizygotes in GnomAd4 at 19 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
H2BW2	NM_001388464.1 link	c.257T>C	p.Ile86Thr	missense_variant	Exon 1 of 4	ENST00000675318.3	NP_001375393.1
H2BW2	NM_001164416.4 link	c.257T>C	p.Ile86Thr	missense_variant	Exon 1 of 3		NP_001157888.2
H2BW2	XM_011530922.3 link	c.275T>C	p.Ile92Thr	missense_variant	Exon 1 of 3		XP_011529224.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
H2BW2	ENST00000675318.3 link	c.257T>C	p.Ile86Thr	missense_variant	Exon 1 of 4		NM_001388464.1	ENSP00000502072.2
H2BW2	ENST00000355016.8 link	c.257T>C	p.Ile86Thr	missense_variant	Exon 1 of 3	2		ENSP00000347119.4
H2BW2	ENST00000417637.1 link	c.-32T>C		upstream_gene_variant		3		ENSP00000402466.1

Frequencies

GnomAD3 genomes

AF:

0.000467

AC:

AN:

111376

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000981

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000283

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000775

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00840

Gnomad NFE

AF:

0.000737

Gnomad OTH

AF:

0.00199

GnomAD2 exomes

AF:

0.000477

AC:

AN:

150934

AF XY:

0.000627

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000494

Gnomad ASJ exome

AF:

0.000145

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000637

Gnomad OTH exome

AF:

0.000752

GnomAD4 exome

AF:

0.000449

AC:

486

AN:

1081416

Hom.:

Cov.:

AF XY:

0.000534

AC XY:

188

AN XY:

352240

show subpopulations

African (AFR)

AF:

0.000154

AC:

AN:

25907

American (AMR)

AF:

0.000485

AC:

AN:

33002

Ashkenazi Jewish (ASJ)

AF:

0.0000524

AC:

AN:

19075

East Asian (EAS)

AF:

0.00

AC:

AN:

29172

South Asian (SAS)

AF:

0.00140

AC:

AN:

51553

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39387

Middle Eastern (MID)

AF:

0.00170

AC:

AN:

4121

European-Non Finnish (NFE)

AF:

0.000431

AC:

359

AN:

833653

Other (OTH)

AF:

0.000593

AC:

AN:

45546

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000458

AC:

AN:

111431

Hom.:

Cov.:

AF XY:

0.000565

AC XY:

AN XY:

33647

show subpopulations

African (AFR)

AF:

0.0000978

AC:

AN:

30664

American (AMR)

AF:

0.000282

AC:

AN:

10623

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2649

East Asian (EAS)

AF:

0.00

AC:

AN:

3504

South Asian (SAS)

AF:

0.000777

AC:

AN:

2573

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6079

Middle Eastern (MID)

AF:

0.00461

AC:

AN:

217

European-Non Finnish (NFE)

AF:

0.000737

AC:

AN:

52910

Other (OTH)

AF:

0.00196

AC:

AN:

1531

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000509

Hom.:

Bravo

AF:

0.000457

ExAC

AF:

0.000491

AC:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:3

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Benign:3

Apr 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

H2BW2: BS2 -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Dec 18, 2017

Genomic Research Center, Shahid Beheshti University of Medical Sciences

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Uncertain:1

May 15, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.275T>C (p.I92T) alteration is located in exon 1 (coding exon 1) of the H2BFM gene. This alteration results from a T to C substitution at nucleotide position 275, causing the isoleucine (I) at amino acid position 92 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

Uncertain

0.44

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.11

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.13

T;T

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.75

.;T

M_CAP

Benign

0.012

MetaRNN

Benign

0.067

T;T

MetaSVM

Benign

-0.70

PhyloP100

6.7

PrimateAI

Uncertain

0.60

PROVEAN

Uncertain

-3.7

D;.

REVEL

Uncertain

0.40

Sift

Uncertain

0.021

D;.

Sift4G

Uncertain

0.038

D;D

Vest4

0.41

MVP

0.95

MPC

0.0029

ClinPred

0.13

GERP RS

1.4

PromoterAI

-0.015

Neutral

(source)

Varity_R

0.17

gMVP

0.31

Mutation Taster

=97/3

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over