6-113944423-T-C

Variant names:

• chr6-113944423-T-C
• rs13204445
• NM_001527.4:c.1092-13A>G

Variant summary

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

The NM_001527.4(HDAC2):​c.1092-13A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.257 in 1,602,446 control chromosomes in the GnomAD database, including 54,861 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 0.22 (3967 hom., cov: 32)
  • Exomes 𝑓: 0.26 (50894 hom.)
• Consequence: HDAC2 NM_001527.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.985
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.291 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HDAC2	NM_001527.4	c.1092-13A>G		intron_variant	Intron 10 of 13	ENST00000519065.6	NP_001518.3
HDAC2	NR_033441.2	n.1360-13A>G		intron_variant	Intron 11 of 14
HDAC2	NR_073443.2	n.1290-13A>G		intron_variant	Intron 10 of 13
HDAC2	XM_047418692.1	c.1002-13A>G		intron_variant	Intron 10 of 13		XP_047274648.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HDAC2	ENST00000519065.6	c.1092-13A>G		intron_variant	Intron 10 of 13	1	NM_001527.4	ENSP00000430432.1
HDAC2	ENST00000368632.6	c.1002-13A>G		intron_variant	Intron 11 of 14	2		ENSP00000357621.2
HDAC2	ENST00000519108.5	c.1002-13A>G		intron_variant	Intron 10 of 13	2		ENSP00000430008.1
HDAC2	ENST00000523334.1	n.4095-13A>G		intron_variant	Intron 4 of 7	2

Frequencies

GnomAD3 genomes AF: 0.222 AC: 33791 AN: 152016 Hom.: 3969 Cov.: 32

Gnomad AFR AF: 0.144

Gnomad AMI AF: 0.219

Gnomad AMR AF: 0.209

Gnomad ASJ AF: 0.278

Gnomad EAS AF: 0.303

Gnomad SAS AF: 0.271

Gnomad FIN AF: 0.195

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.264

Gnomad OTH AF: 0.239

GnomAD2 exomes AF: 0.236 AC: 57597 AN: 243982 AF XY: 0.243

Gnomad AFR exome AF: 0.139

Gnomad AMR exome AF: 0.145

Gnomad ASJ exome AF: 0.272

Gnomad EAS exome AF: 0.300

Gnomad FIN exome AF: 0.202

Gnomad NFE exome AF: 0.260

Gnomad OTH exome AF: 0.256

GnomAD4 exome AF: 0.261 AC: 378196 AN: 1450312 Hom.: 50894 Cov.: 29 AF XY: 0.262 AC XY: 189167 AN XY: 721798

African (AFR) AF: 0.140 AC: 4621 AN: 33074

American (AMR) AF: 0.150 AC: 6447 AN: 43120

Ashkenazi Jewish (ASJ) AF: 0.275 AC: 7135 AN: 25920

East Asian (EAS) AF: 0.305 AC: 12099 AN: 39622

South Asian (SAS) AF: 0.267 AC: 22684 AN: 85060

European-Finnish (FIN) AF: 0.200 AC: 10690 AN: 53384

Middle Eastern (MID) AF: 0.291 AC: 1668 AN: 5740

European-Non Finnish (NFE) AF: 0.269 AC: 296558 AN: 1104396

Other (OTH) AF: 0.272 AC: 16294 AN: 59996

GnomAD4 genome AF: 0.222 AC: 33795 AN: 152134 Hom.: 3967 Cov.: 32 AF XY: 0.221 AC XY: 16410 AN XY: 74380

African (AFR) AF: 0.144 AC: 5966 AN: 41510

American (AMR) AF: 0.209 AC: 3193 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.278 AC: 966 AN: 3472

East Asian (EAS) AF: 0.304 AC: 1571 AN: 5176

South Asian (SAS) AF: 0.273 AC: 1316 AN: 4822

European-Finnish (FIN) AF: 0.195 AC: 2060 AN: 10584

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.264 AC: 17930 AN: 67964

Other (OTH) AF: 0.240 AC: 507 AN: 2116

Alfa AF: 0.191 Hom.: 715

Bravo AF: 0.218

Asia WGS AF: 0.296 AC: 1029 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.12
DANN	Benign	0.65
PhyloP100		-0.98
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: rs13204445; hg19: chr6-114265587; COSMIC: COSV64039338; COSMIC: COSV64039338;