6-113944423-T-C

Position:

• chr6-113944423-T-C

Variant summary

Our verdict is Benign. Variant got -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

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
HDAC2	NM_001527.4	c.1092-13A>G		intron_variant		ENST00000519065.6	NP_001518.3
HDAC2	XM_047418692.1	c.1002-13A>G		intron_variant			XP_047274648.1
HDAC2	NR_033441.2	n.1360-13A>G		intron_variant
HDAC2	NR_073443.2	n.1290-13A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HDAC2	ENST00000519065.6	c.1092-13A>G		intron_variant		1	NM_001527.4	ENSP00000430432.1
HDAC2	ENST00000368632.6	c.1002-13A>G		intron_variant		2		ENSP00000357621.2
HDAC2	ENST00000519108.5	c.1002-13A>G		intron_variant		2		ENSP00000430008.1
HDAC2	ENST00000523334.1	n.4095-13A>G		intron_variant		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

GnomAD3 exomes AF: 0.236 AC: 57597 AN: 243982 Hom.: 7200 AF XY: 0.243 AC XY: 32225 AN XY: 132396

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 SAS exome AF: 0.269

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

Gnomad4 AFR exome AF: 0.140

Gnomad4 AMR exome AF: 0.150

Gnomad4 ASJ exome AF: 0.275

Gnomad4 EAS exome AF: 0.305

Gnomad4 SAS exome AF: 0.267

Gnomad4 FIN exome AF: 0.200

Gnomad4 NFE exome AF: 0.269

Gnomad4 OTH exome AF: 0.272

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

Gnomad4 AFR AF: 0.144

Gnomad4 AMR AF: 0.209

Gnomad4 ASJ AF: 0.278

Gnomad4 EAS AF: 0.304

Gnomad4 SAS AF: 0.273

Gnomad4 FIN AF: 0.195

Gnomad4 NFE AF: 0.264

Gnomad4 OTH AF: 0.240

Alfa AF: 0.192 Hom.: 710

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

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

LitVar

Other links and lift over

dbSNP: rs13204445; hg19: chr6-114265587; COSMIC: COSV64039338; COSMIC: COSV64039338;