chr6-113941763-C-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001527.4(HDAC2):c.1381G>A(p.Val461Ile) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000344 in 1,338,954 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000037 ( 0 hom. )

Consequence

HDAC2
NM_001527.4 missense, splice_region

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.83

Publications

1 publications found

Variant links:

Genes affected

HDAC2 (HGNC:4853): (histone deacetylase 2) This gene product belongs to the histone deacetylase family. Histone deacetylases act via the formation of large multiprotein complexes, and are responsible for the deacetylation of lysine residues at the N-terminal regions of core histones (H2A, H2B, H3 and H4). This protein forms transcriptional repressor complexes by associating with many different proteins, including YY1, a mammalian zinc-finger transcription factor. Thus, it plays an important role in transcriptional regulation, cell cycle progression and developmental events. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2010]

HDAC2 Gene-Disease associations (from GenCC):

complex neurodevelopmental disorder
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

HDAC2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.11321136).

BS2

High AC in GnomAdExome4 at 44 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001527.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HDAC2	NM_001527.4	MANE Select	c.1381G>A	p.Val461Ile	missense splice_region	Exon 13 of 14	NP_001518.3	Q92769-1
HDAC2	NR_033441.2		n.1649G>A		splice_region non_coding_transcript_exon	Exon 14 of 15
HDAC2	NR_073443.2		n.1579G>A		splice_region non_coding_transcript_exon	Exon 13 of 14

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HDAC2	ENST00000519065.6	TSL:1 MANE Select	c.1381G>A	p.Val461Ile	missense splice_region	Exon 13 of 14	ENSP00000430432.1	Q92769-1
HDAC2	ENST00000916847.1		c.1420G>A	p.Val474Ile	missense splice_region	Exon 13 of 14	ENSP00000586906.1
HDAC2	ENST00000869750.1		c.1405G>A	p.Val469Ile	missense splice_region	Exon 13 of 14	ENSP00000539809.1

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151760

Hom.:

Cov.:

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:

0.0000295

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000159

AC:

AN:

188722

AF XY:

0.00000963

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000338

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000371

AC:

AN:

1187194

Hom.:

Cov.:

AF XY:

0.0000234

AC XY:

AN XY:

597340

show subpopulations

African (AFR)

AF:

0.0000387

AC:

AN:

25808

American (AMR)

AF:

0.00

AC:

AN:

33002

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21876

East Asian (EAS)

AF:

0.00

AC:

AN:

34196

South Asian (SAS)

AF:

0.00

AC:

AN:

63538

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49884

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3782

European-Non Finnish (NFE)

AF:

0.0000453

AC:

AN:

905350

Other (OTH)

AF:

0.0000402

AC:

AN:

49758

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

GnomAD4 genome

AF:

0.0000132

AC:

AN:

151760

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74104

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41356

American (AMR)

AF:

0.00

AC:

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.00

AC:

AN:

4812

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10502

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000295

AC:

AN:

67854

Other (OTH)

AF:

0.00

AC:

AN:

2084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.00

Hom.:

Bravo

AF:

0.0000189

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.41

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.32

Eigen

Benign

-0.16

Eigen_PC

Benign

0.075

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.84

M_CAP

Benign

0.022

MetaRNN

Benign

0.11

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.81

PhyloP100

2.8

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-0.25

REVEL

Benign

0.17

Sift

Benign

0.39

Sift4G

Benign

0.33

Polyphen

0.0010

Vest4

0.27

MutPred

0.14

Loss of methylation at K462 (P = 0.091)

MVP

0.62

MPC

0.33

ClinPred

0.20

GERP RS

5.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.075

gMVP

0.070

Mutation Taster

=85/15

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over