Genetic Variant NM_001527.4:c.1414G>A (chr6-113941730-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001527.4(HDAC2):c.1414G>A(p.Gly472Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000154 in 1,296,652 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000015 ( 0 hom. )

Consequence

HDAC2
NM_001527.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.35

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: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14014068).

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.1414G>A	p.Gly472Ser	missense	Exon 13 of 14	NP_001518.3	Q92769-1
HDAC2	NR_033441.2		n.1682G>A		non_coding_transcript_exon	Exon 14 of 15
HDAC2	NR_073443.2		n.1612G>A		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.1414G>A	p.Gly472Ser	missense	Exon 13 of 14	ENSP00000430432.1	Q92769-1
HDAC2	ENST00000916847.1		c.1453G>A	p.Gly485Ser	missense	Exon 13 of 14	ENSP00000586906.1
HDAC2	ENST00000869750.1		c.1438G>A	p.Gly480Ser	missense	Exon 13 of 14	ENSP00000539809.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000487

AC:

AN:

205204

AF XY:

0.00

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:

0.0000104

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000154

AC:

AN:

1296652

Hom.:

Cov.:

AF XY:

0.00000154

AC XY:

AN XY:

649944

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

28268

American (AMR)

AF:

0.00

AC:

AN:

35982

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23408

East Asian (EAS)

AF:

0.00

AC:

AN:

35622

South Asian (SAS)

AF:

0.00

AC:

AN:

71762

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51346

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4374

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

992122

Other (OTH)

AF:

0.0000372

AC:

AN:

53768

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000936

Hom.:

Asia WGS

AF:

0.000578

AC:

AN:

3474

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

0.062

BayesDel_addAF

Benign

-0.054

BayesDel_noAF

Benign

-0.32

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.28

Eigen

Benign

-0.14

Eigen_PC

Benign

0.086

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.85

M_CAP

Benign

0.0090

MetaRNN

Benign

0.14

MetaSVM

Benign

-0.89

MutationAssessor

Benign

0.34

PhyloP100

2.4

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-0.58

REVEL

Benign

0.18

Sift

Benign

0.21

Sift4G

Benign

0.49

Polyphen

0.0

Vest4

0.23

MutPred

0.21

Gain of phosphorylation at G472 (P = 9e-04)

MVP

0.65

MPC

0.40

ClinPred

0.22

GERP RS

5.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.098

gMVP

0.16

Mutation Taster

=81/19

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over