Variant 6-113944342-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_001527.4(HDAC2):c.1160A>G(p.Glu387Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0000118 in 1,613,036 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

HDAC2
NM_001527.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.00

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.3628893).

BS2

High AC in GnomAdExome4 at 18 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HDAC2	NM_001527.4 link	c.1160A>G	p.Glu387Gly	missense_variant	Exon 11 of 14	ENST00000519065.6	NP_001518.3	Q92769-1
HDAC2	XM_047418692.1 link	c.1070A>G	p.Glu357Gly	missense_variant	Exon 11 of 14		XP_047274648.1
HDAC2	NR_033441.2 link	n.1428A>G		non_coding_transcript_exon_variant	Exon 12 of 15
HDAC2	NR_073443.2 link	n.1358A>G		non_coding_transcript_exon_variant	Exon 11 of 14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
HDAC2	ENST00000519065.6 link	c.1160A>G	p.Glu387Gly	missense_variant	Exon 11 of 14	1	NM_001527.4	ENSP00000430432.1	Q92769-1
HDAC2	ENST00000368632.6 link	c.1070A>G	p.Glu357Gly	missense_variant	Exon 12 of 15	2		ENSP00000357621.2	Q92769-3
HDAC2	ENST00000519108.5 link	c.1070A>G	p.Glu357Gly	missense_variant	Exon 11 of 14	2		ENSP00000430008.1	Q92769-3
HDAC2	ENST00000523334.1 link	n.4163A>G		non_coding_transcript_exon_variant	Exon 5 of 8	2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152192

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000123

AC:

AN:

1460844

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

726820

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:

0.0000153

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152192

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74366

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:

0.0000147

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

Dec 09, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1160A>G (p.E387G) alteration is located in exon 11 (coding exon 11) of the HDAC2 gene. This alteration results from a A to G substitution at nucleotide position 1160, causing the glutamic acid (E) at amino acid position 387 to be replaced by a glycine (G). 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

0.29

BayesDel_addAF

Pathogenic

0.19

BayesDel_noAF

Uncertain

0.030

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.68

D;.;.

Eigen

Uncertain

0.51

Eigen_PC

Uncertain

0.58

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.94

D;.;D

M_CAP

Benign

0.084

MetaRNN

Benign

0.36

T;T;T

MetaSVM

Uncertain

-0.14

MutationAssessor

Benign

1.9

M;.;.

PrimateAI

Pathogenic

0.82

PROVEAN

Uncertain

-2.7

D;D;D

REVEL

Uncertain

0.43

Sift

Benign

0.090

T;T;T

Sift4G

Benign

0.18

T;T;T

Polyphen

1.0

D;.;.

Vest4

0.31

MutPred

0.29

Loss of solvent accessibility (P = 0.0769);.;.;

MVP

0.77

MPC

0.48

ClinPred

0.77

GERP RS

6.1

Varity_R

0.26

gMVP

0.34

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