rs2475631

Variant names:

• chr6-113956461-T-C
• rs2475631
• NM_001527.4:c.358+158A>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.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
• Publications: 5 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 (AMR) allele frequency at 95% confidence interval = 0.364 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001527.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HDAC2	NM_001527.4	MANE Select	c.358+158A>G		intron	N/A	NP_001518.3	Q92769-1
	HDAC2	NR_033441.2		n.626+158A>G		intron	N/A
	HDAC2	NR_073443.2		n.556+158A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HDAC2	ENST00000519065.6	TSL:1 MANE Select	c.358+158A>G		intron	N/A	ENSP00000430432.1	Q92769-1
	HDAC2	ENST00000916847.1		c.358+158A>G		intron	N/A	ENSP00000586906.1
	HDAC2	ENST00000869750.1		c.358+158A>G		intron	N/A	ENSP00000539809.1

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

African (AFR) AF: 0.223 AC: 2831 AN: 12672

American (AMR) AF: 0.394 AC: 7005 AN: 17770

Ashkenazi Jewish (ASJ) AF: 0.319 AC: 4382 AN: 13718

East Asian (EAS) AF: 0.316 AC: 9814 AN: 31070

South Asian (SAS) AF: 0.342 AC: 13581 AN: 39752

European-Finnish (FIN) AF: 0.350 AC: 13434 AN: 38404

Middle Eastern (MID) AF: 0.347 AC: 1126 AN: 3248

European-Non Finnish (NFE) AF: 0.353 AC: 97932 AN: 277390

Other (OTH) AF: 0.327 AC: 8550 AN: 26108

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

African (AFR) AF: 0.220 AC: 9131 AN: 41518

American (AMR) AF: 0.372 AC: 5692 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.315 AC: 1092 AN: 3470

East Asian (EAS) AF: 0.292 AC: 1510 AN: 5174

South Asian (SAS) AF: 0.329 AC: 1588 AN: 4830

European-Finnish (FIN) AF: 0.358 AC: 3783 AN: 10570

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.354 AC: 24059 AN: 67962

Other (OTH) AF: 0.322 AC: 680 AN: 2110

Alfa AF: 0.321 Hom.: 1026

Bravo AF: 0.311

Asia WGS AF: 0.275 AC: 957 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.018
DANN	Benign	0.63
PhyloP100		-3.9
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: rs2475631; hg19: chr6-114277625; COSMIC: COSV107473754; COSMIC: COSV107473754;