rs2475631

Positions:

• chr6-113956461-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.358+158A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.337 in 612,260 control chromosomes in the GnomAD database, including 35,872 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 0.31 (7852 hom., cov: 33)
  • Exomes 𝑓: 0.34 (28020 hom.)
• Consequence: HDAC2 NM_001527.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.86

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.364 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HDAC2	NM_001527.4	c.358+158A>G		intron_variant		ENST00000519065.6	NP_001518.3
HDAC2	XM_047418692.1	c.268+158A>G		intron_variant			XP_047274648.1
HDAC2	NR_033441.2	n.626+158A>G		intron_variant, non_coding_transcript_variant
HDAC2	NR_073443.2	n.556+158A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HDAC2	ENST00000519065.6	c.358+158A>G		intron_variant		1	NM_001527.4	ENSP00000430432	P1

Frequencies

GnomAD3 genomes AF: 0.315 AC: 47827 AN: 152010 Hom.: 7847 Cov.: 33

Gnomad AFR AF: 0.220

Gnomad AMI AF: 0.254

Gnomad AMR AF: 0.372

Gnomad ASJ AF: 0.315

Gnomad EAS AF: 0.292

Gnomad SAS AF: 0.329

Gnomad FIN AF: 0.358

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.354

Gnomad OTH AF: 0.325

GnomAD4 exome AF: 0.345 AC: 158655 AN: 460132 Hom.: 28020 Cov.: 5 AF XY: 0.345 AC XY: 83392 AN XY: 241578

Gnomad4 AFR exome AF: 0.223

Gnomad4 AMR exome AF: 0.394

Gnomad4 ASJ exome AF: 0.319

Gnomad4 EAS exome AF: 0.316

Gnomad4 SAS exome AF: 0.342

Gnomad4 FIN exome AF: 0.350

Gnomad4 NFE exome AF: 0.353

Gnomad4 OTH exome AF: 0.327

GnomAD4 genome AF: 0.314 AC: 47843 AN: 152128 Hom.: 7852 Cov.: 33 AF XY: 0.315 AC XY: 23437 AN XY: 74374

Gnomad4 AFR AF: 0.220

Gnomad4 AMR AF: 0.372

Gnomad4 ASJ AF: 0.315

Gnomad4 EAS AF: 0.292

Gnomad4 SAS AF: 0.329

Gnomad4 FIN AF: 0.358

Gnomad4 NFE AF: 0.354

Gnomad4 OTH AF: 0.322

Alfa AF: 0.325 Hom.: 1005

Bravo AF: 0.311

Asia WGS AF: 0.275 AC: 957 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	0.018
DANN	Benign	0.63

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: rs2475631; hg19: chr6-114277625;