6-113954346-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001527.4(HDAC2):c.498-928G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.291 in 151,890 control chromosomes in the GnomAD database, including 6,554 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 0.29 (6554 hom., cov: 33)
• Consequence: HDAC2 NM_001527.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.880

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.362 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HDAC2	NM_001527.4	c.498-928G>C		intron_variant		ENST00000519065.6
HDAC2	XM_047418692.1	c.408-928G>C		intron_variant
HDAC2	NR_033441.2	n.766-928G>C		intron_variant, non_coding_transcript_variant
HDAC2	NR_073443.2	n.696-928G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HDAC2	ENST00000519065.6	c.498-928G>C		intron_variant		1	NM_001527.4	P1

Frequencies

GnomAD3 genomes AF: 0.291 AC: 44117 AN: 151772 Hom.: 6533 Cov.: 33

Gnomad AFR AF: 0.253

Gnomad AMI AF: 0.350

Gnomad AMR AF: 0.312

Gnomad ASJ AF: 0.264

Gnomad EAS AF: 0.376

Gnomad SAS AF: 0.360

Gnomad FIN AF: 0.307

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.295

Gnomad OTH AF: 0.300

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

GnomAD4 genome AF: 0.291 AC: 44197 AN: 151890 Hom.: 6554 Cov.: 33 AF XY: 0.293 AC XY: 21769 AN XY: 74220

Gnomad4 AFR AF: 0.253

Gnomad4 AMR AF: 0.313

Gnomad4 ASJ AF: 0.264

Gnomad4 EAS AF: 0.376

Gnomad4 SAS AF: 0.359

Gnomad4 FIN AF: 0.307

Gnomad4 NFE AF: 0.295

Gnomad4 OTH AF: 0.304

Alfa AF: 0.160 Hom.: 303

Bravo AF: 0.291

Asia WGS AF: 0.374 AC: 1303 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.35
Dann	Benign	0.34
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs9488289; hg19: chr6-114275510; COSMIC: COSV64037638; COSMIC: COSV64037638;