6-113949764-C-T

Variant names:

• chr6-113949764-C-T
• rs6568819
• NM_001527.4:c.640-504G>A

Variant summary

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

The NM_001527.4(HDAC2):​c.640-504G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 151,952 control chromosomes in the GnomAD database, including 2,743 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 0.18 (2743 hom., cov: 32)
• Consequence: HDAC2 NM_001527.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0340
• Publications: 14 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.343 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HDAC2	NM_001527.4	c.640-504G>A		intron_variant	Intron 6 of 13	ENST00000519065.6	NP_001518.3
HDAC2	NR_033441.2	n.908-504G>A		intron_variant	Intron 7 of 14
HDAC2	NR_073443.2	n.838-504G>A		intron_variant	Intron 6 of 13
HDAC2	XM_047418692.1	c.550-504G>A		intron_variant	Intron 6 of 13		XP_047274648.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HDAC2	ENST00000519065.6	c.640-504G>A		intron_variant	Intron 6 of 13	1	NM_001527.4	ENSP00000430432.1
HDAC2	ENST00000368632.6	c.550-504G>A		intron_variant	Intron 7 of 14	2		ENSP00000357621.2
HDAC2	ENST00000519108.5	c.550-504G>A		intron_variant	Intron 6 of 13	2		ENSP00000430008.1
HDAC2	ENST00000523334.1	n.733-504G>A		intron_variant	Intron 2 of 7	2

Frequencies

GnomAD3 genomes AF: 0.181 AC: 27487 AN: 151834 Hom.: 2740 Cov.: 32

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.203

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.216

Gnomad EAS AF: 0.356

Gnomad SAS AF: 0.228

Gnomad FIN AF: 0.226

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.196

Gnomad OTH AF: 0.187

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

GnomAD4 genome AF: 0.181 AC: 27509 AN: 151952 Hom.: 2743 Cov.: 32 AF XY: 0.184 AC XY: 13652 AN XY: 74284

African (AFR) AF: 0.114 AC: 4705 AN: 41450

American (AMR) AF: 0.184 AC: 2803 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.216 AC: 749 AN: 3470

East Asian (EAS) AF: 0.356 AC: 1842 AN: 5170

South Asian (SAS) AF: 0.227 AC: 1094 AN: 4810

European-Finnish (FIN) AF: 0.226 AC: 2380 AN: 10512

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.196 AC: 13294 AN: 67958

Other (OTH) AF: 0.192 AC: 405 AN: 2110

Alfa AF: 0.192 Hom.: 3763

Bravo AF: 0.178

Asia WGS AF: 0.287 AC: 997 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	2.8
DANN	Benign	0.74
PhyloP100		-0.034
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: rs6568819; hg19: chr6-114270928;