rs11391

Positions:

• chr6-113940851-A-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001527.4(HDAC2):​c.*207T>G variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.104 in 465,432 control chromosomes in the GnomAD database, including 2,867 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 0.092 (794 hom., cov: 32)
  • Exomes 𝑓: 0.11 (2073 hom.)
• Consequence: HDAC2 NM_001527.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.17

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.121 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HDAC2	NM_001527.4	c.*207T>G		3_prime_UTR_variant	14/14	ENST00000519065.6
HDAC2	XM_047418692.1	c.*207T>G		3_prime_UTR_variant	14/14
HDAC2	NR_033441.2	n.1942T>G		non_coding_transcript_exon_variant	15/15
HDAC2	NR_073443.2	n.1872T>G		non_coding_transcript_exon_variant	14/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HDAC2	ENST00000519065.6	c.*207T>G		3_prime_UTR_variant	14/14	1	NM_001527.4	P1
HDAC2	ENST00000368632.6	c.*207T>G		3_prime_UTR_variant	15/15	2
HDAC2	ENST00000519108.5	c.*207T>G		3_prime_UTR_variant	14/14	2
HDAC2	ENST00000523334.1	n.4677T>G		non_coding_transcript_exon_variant	8/8	2

Frequencies

GnomAD3 genomes AF: 0.0919 AC: 13968 AN: 152006 Hom.: 789 Cov.: 32

Gnomad AFR AF: 0.0265

Gnomad AMI AF: 0.140

Gnomad AMR AF: 0.0777

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.0781

Gnomad SAS AF: 0.118

Gnomad FIN AF: 0.156

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.123

Gnomad OTH AF: 0.0938

GnomAD4 exome AF: 0.111 AC: 34652 AN: 313308 Hom.: 2073 Cov.: 3 AF XY: 0.111 AC XY: 18346 AN XY: 164572

Gnomad4 AFR exome AF: 0.0239

Gnomad4 AMR exome AF: 0.0842

Gnomad4 ASJ exome AF: 0.112

Gnomad4 EAS exome AF: 0.0841

Gnomad4 SAS exome AF: 0.105

Gnomad4 FIN exome AF: 0.149

Gnomad4 NFE exome AF: 0.117

Gnomad4 OTH exome AF: 0.100

GnomAD4 genome AF: 0.0919 AC: 13974 AN: 152124 Hom.: 794 Cov.: 32 AF XY: 0.0934 AC XY: 6943 AN XY: 74360

Gnomad4 AFR AF: 0.0265

Gnomad4 AMR AF: 0.0775

Gnomad4 ASJ AF: 0.111

Gnomad4 EAS AF: 0.0779

Gnomad4 SAS AF: 0.117

Gnomad4 FIN AF: 0.156

Gnomad4 NFE AF: 0.123

Gnomad4 OTH AF: 0.0994

Alfa AF: 0.111 Hom.: 611

Bravo AF: 0.0836

Asia WGS AF: 0.100 AC: 345 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	18
DANN	Benign	0.88
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs11391; hg19: chr6-114262015;