6-113952482-C-T

Variant names:

• chr6-113952482-C-T
• rs10499080
• NM_001527.4:c.639+795G>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.639+795G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0855 in 152,222 control chromosomes in the GnomAD database, including 703 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 0.085 (703 hom., cov: 33)
• Consequence: HDAC2 NM_001527.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.58
• Publications: 10 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.265 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HDAC2	NM_001527.4	c.639+795G>A		intron_variant	Intron 6 of 13	ENST00000519065.6	NP_001518.3
HDAC2	NR_033441.2	n.907+795G>A		intron_variant	Intron 7 of 14
HDAC2	NR_073443.2	n.837+795G>A		intron_variant	Intron 6 of 13
HDAC2	XM_047418692.1	c.549+795G>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.639+795G>A		intron_variant	Intron 6 of 13	1	NM_001527.4	ENSP00000430432.1
HDAC2	ENST00000368632.6	c.549+795G>A		intron_variant	Intron 7 of 14	2		ENSP00000357621.2
HDAC2	ENST00000519108.5	c.549+795G>A		intron_variant	Intron 6 of 13	2		ENSP00000430008.1
HDAC2	ENST00000523334.1	n.732+795G>A		intron_variant	Intron 2 of 7	2

Frequencies

GnomAD3 genomes AF: 0.0855 AC: 12998 AN: 152102 Hom.: 701 Cov.: 33

Gnomad AFR AF: 0.0754

Gnomad AMI AF: 0.0625

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.276

Gnomad SAS AF: 0.110

Gnomad FIN AF: 0.0694

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.0725

Gnomad OTH AF: 0.0912

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

GnomAD4 genome AF: 0.0855 AC: 13012 AN: 152222 Hom.: 703 Cov.: 33 AF XY: 0.0867 AC XY: 6453 AN XY: 74426

African (AFR) AF: 0.0752 AC: 3124 AN: 41534

American (AMR) AF: 0.105 AC: 1606 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.105 AC: 365 AN: 3470

East Asian (EAS) AF: 0.277 AC: 1431 AN: 5174

South Asian (SAS) AF: 0.110 AC: 532 AN: 4826

European-Finnish (FIN) AF: 0.0694 AC: 735 AN: 10594

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.0725 AC: 4929 AN: 68010

Other (OTH) AF: 0.0907 AC: 192 AN: 2116

Alfa AF: 0.0778 Hom.: 1090

Bravo AF: 0.0904

Asia WGS AF: 0.186 AC: 644 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.23
DANN	Benign	0.55
PhyloP100		-1.6
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: rs10499080; hg19: chr6-114273646;