6-113940851-A-C

Variant names:

• chr6-113940851-A-C
• rs11391
• NM_001527.4:c.*207T>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 12 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 -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 rank	MANE	Protein	UniProt
HDAC2	NM_001527.4	c.*207T>G		3_prime_UTR_variant	Exon 14 of 14	ENST00000519065.6	NP_001518.3
HDAC2	NR_033441.2	n.1942T>G		non_coding_transcript_exon_variant	Exon 15 of 15
HDAC2	NR_073443.2	n.1872T>G		non_coding_transcript_exon_variant	Exon 14 of 14
HDAC2	XM_047418692.1	c.*207T>G		3_prime_UTR_variant	Exon 14 of 14		XP_047274648.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HDAC2	ENST00000519065.6	c.*207T>G		3_prime_UTR_variant	Exon 14 of 14	1	NM_001527.4	ENSP00000430432.1
HDAC2	ENST00000523334.1	n.4677T>G		non_coding_transcript_exon_variant	Exon 8 of 8	2
HDAC2	ENST00000368632.6	c.*207T>G		3_prime_UTR_variant	Exon 15 of 15	2		ENSP00000357621.2
HDAC2	ENST00000519108.5	c.*207T>G		3_prime_UTR_variant	Exon 14 of 14	2		ENSP00000430008.1

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

African (AFR) AF: 0.0239 AC: 215 AN: 8980

American (AMR) AF: 0.0842 AC: 899 AN: 10678

Ashkenazi Jewish (ASJ) AF: 0.112 AC: 1176 AN: 10466

East Asian (EAS) AF: 0.0841 AC: 2128 AN: 25314

South Asian (SAS) AF: 0.105 AC: 2062 AN: 19602

European-Finnish (FIN) AF: 0.149 AC: 3322 AN: 22236

Middle Eastern (MID) AF: 0.0770 AC: 114 AN: 1480

European-Non Finnish (NFE) AF: 0.117 AC: 22832 AN: 195538

Other (OTH) AF: 0.100 AC: 1904 AN: 19014

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

African (AFR) AF: 0.0265 AC: 1100 AN: 41564

American (AMR) AF: 0.0775 AC: 1185 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.111 AC: 384 AN: 3472

East Asian (EAS) AF: 0.0779 AC: 404 AN: 5186

South Asian (SAS) AF: 0.117 AC: 565 AN: 4814

European-Finnish (FIN) AF: 0.156 AC: 1648 AN: 10564

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.123 AC: 8339 AN: 67916

Other (OTH) AF: 0.0994 AC: 210 AN: 2112

Alfa AF: 0.0994 Hom.: 811

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
PhyloP100		4.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11391; hg19: chr6-114262015;