6-113954346-C-G

Variant names:

• chr6-113954346-C-G
• rs9488289
• NM_001527.4:c.498-928G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001527.4(HDAC2):​c.498-928G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.291 in 151,890 control chromosomes in the GnomAD database, including 6,554 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 0.29 (6554 hom., cov: 33)
• Consequence: HDAC2 NM_001527.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.880
• Publications: 4 publications found

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.362 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HDAC2	NM_001527.4	MANE Select	c.498-928G>C		intron	N/A	NP_001518.3
	HDAC2	NR_033441.2		n.766-928G>C		intron	N/A
	HDAC2	NR_073443.2		n.696-928G>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HDAC2	ENST00000519065.6	TSL:1 MANE Select	c.498-928G>C		intron	N/A	ENSP00000430432.1
	HDAC2	ENST00000916847.1		c.498-928G>C		intron	N/A	ENSP00000586906.1
	HDAC2	ENST00000869750.1		c.522-928G>C		intron	N/A	ENSP00000539809.1

Frequencies

GnomAD3 genomes AF: 0.291 AC: 44117 AN: 151772 Hom.: 6533 Cov.: 33

Gnomad AFR AF: 0.253

Gnomad AMI AF: 0.350

Gnomad AMR AF: 0.312

Gnomad ASJ AF: 0.264

Gnomad EAS AF: 0.376

Gnomad SAS AF: 0.360

Gnomad FIN AF: 0.307

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.295

Gnomad OTH AF: 0.300

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.291 AC: 44197 AN: 151890 Hom.: 6554 Cov.: 33 AF XY: 0.293 AC XY: 21769 AN XY: 74220

African (AFR) AF: 0.253 AC: 10491 AN: 41410

American (AMR) AF: 0.313 AC: 4774 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.264 AC: 916 AN: 3470

East Asian (EAS) AF: 0.376 AC: 1943 AN: 5162

South Asian (SAS) AF: 0.359 AC: 1728 AN: 4820

European-Finnish (FIN) AF: 0.307 AC: 3227 AN: 10522

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.295 AC: 20069 AN: 67940

Other (OTH) AF: 0.304 AC: 641 AN: 2112

Alfa AF: 0.160 Hom.: 303

Bravo AF: 0.291

Asia WGS AF: 0.374 AC: 1303 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.35
DANN	Benign	0.34
PhyloP100		-0.88
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9488289; hg19: chr6-114275510; COSMIC: COSV64037638; COSMIC: COSV64037638;