Genetic Variant NM_001527.4:c.358+158A>G (chr6-113956461-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001527.4(HDAC2):c.358+158A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.337 in 612,260 control chromosomes in the GnomAD database, including 35,872 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.31 ( 7852 hom., cov: 33)

Exomes 𝑓: 0.34 ( 28020 hom. )

Consequence

HDAC2
NM_001527.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.86

Publications

5 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: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.364 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
HDAC2	NM_001527.4 link	c.358+158A>G	intron_variant	Intron 4 of 13	ENST00000519065.6	NP_001518.3	Q92769-1
HDAC2	NR_033441.2 link	n.626+158A>G	intron_variant	Intron 5 of 14
HDAC2	NR_073443.2 link	n.556+158A>G	intron_variant	Intron 4 of 13
HDAC2	XM_047418692.1 link	c.268+158A>G	intron_variant	Intron 4 of 13		XP_047274648.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HDAC2	ENST00000519065.6 link	c.358+158A>G		intron_variant	Intron 4 of 13	1	NM_001527.4	ENSP00000430432.1		Q92769-1

Frequencies

GnomAD3 genomes

AF:

0.315

AC:

47827

AN:

152010

Hom.:

7847

Cov.:

show subpopulations

Gnomad AFR

AF:

0.220

Gnomad AMI

AF:

0.254

Gnomad AMR

AF:

0.372

Gnomad ASJ

AF:

0.315

Gnomad EAS

AF:

0.292

Gnomad SAS

AF:

0.329

Gnomad FIN

AF:

0.358

Gnomad MID

AF:

0.263

Gnomad NFE

AF:

0.354

Gnomad OTH

AF:

0.325

GnomAD4 exome

AF:

0.345

AC:

158655

AN:

460132

Hom.:

28020

Cov.:

AF XY:

0.345

AC XY:

83392

AN XY:

241578

show subpopulations

African (AFR)

AF:

0.223

AC:

2831

AN:

12672

American (AMR)

AF:

0.394

AC:

7005

AN:

17770

Ashkenazi Jewish (ASJ)

AF:

0.319

AC:

4382

AN:

13718

East Asian (EAS)

AF:

0.316

AC:

9814

AN:

31070

South Asian (SAS)

AF:

0.342

AC:

13581

AN:

39752

European-Finnish (FIN)

AF:

0.350

AC:

13434

AN:

38404

Middle Eastern (MID)

AF:

0.347

AC:

1126

AN:

3248

European-Non Finnish (NFE)

AF:

0.353

AC:

97932

AN:

277390

Other (OTH)

AF:

0.327

AC:

8550

AN:

26108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

5131

10262

15393

20524

25655

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

720

1440

2160

2880

3600

<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:

0.314

AC:

47843

AN:

152128

Hom.:

7852

Cov.:

AF XY:

0.315

AC XY:

23437

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.220

AC:

9131

AN:

41518

American (AMR)

AF:

0.372

AC:

5692

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.315

AC:

1092

AN:

3470

East Asian (EAS)

AF:

0.292

AC:

1510

AN:

5174

South Asian (SAS)

AF:

0.329

AC:

1588

AN:

4830

European-Finnish (FIN)

AF:

0.358

AC:

3783

AN:

10570

Middle Eastern (MID)

AF:

0.262

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.354

AC:

24059

AN:

67962

Other (OTH)

AF:

0.322

AC:

680

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1708

3415

5123

6830

8538

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

488

976

1464

1952

2440

<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:

0.321

Hom.:

1026

Bravo

AF:

0.311

Asia WGS

AF:

0.275

AC:

957

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.018

(source)

DANN

Benign

0.63

PhyloP100

-3.9

Mutation Taster

=100/0

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over