rs77438668

Variant names:

• chr6-113946123-T-A
• rs77438668
• NM_001527.4:c.867A>T

Your query was ambiguous. Multiple possible variants found:

• chr6-113946123-T-A
• chr6-113946123-T-C

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_001527.4(HDAC2):​c.867A>T​(p.Val289Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000505 in 1,613,470 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0014 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00041 (1 hom.)
• Consequence: HDAC2 NM_001527.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0460
• Publications: 1 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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BP6: Variant 6-113946123-T-A is Benign according to our data. Variant chr6-113946123-T-A is described in ClinVar as Benign. ClinVar VariationId is 782745.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.046 with no splicing effect.
• BS2: High AC in GnomAd4 at 220 AD gene.

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.867A>T	p.Val289Val	synonymous	Exon 9 of 14	NP_001518.3	Q92769-1
	HDAC2	NR_033441.2		n.1135A>T		non_coding_transcript_exon	Exon 10 of 15
	HDAC2	NR_073443.2		n.1065A>T		non_coding_transcript_exon	Exon 9 of 14

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HDAC2	ENST00000519065.6	TSL:1 MANE Select	c.867A>T	p.Val289Val	synonymous	Exon 9 of 14	ENSP00000430432.1	Q92769-1
	HDAC2	ENST00000916847.1		c.906A>T	p.Val302Val	synonymous	Exon 9 of 14	ENSP00000586906.1
	HDAC2	ENST00000869750.1		c.891A>T	p.Val297Val	synonymous	Exon 9 of 14	ENSP00000539809.1

Frequencies

GnomAD3 genomes AF: 0.00144 AC: 219 AN: 152212 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00446

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000785

Gnomad ASJ AF: 0.00231

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000783 AC: 195 AN: 249164 AF XY: 0.000614

Gnomad AFR exome AF: 0.00414

Gnomad AMR exome AF: 0.00139

Gnomad ASJ exome AF: 0.00378

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000319

Gnomad OTH exome AF: 0.00132

GnomAD4 exome AF: 0.000407 AC: 595 AN: 1461140 Hom.: 1 Cov.: 29 AF XY: 0.000351 AC XY: 255 AN XY: 726894

African (AFR) AF: 0.00520 AC: 174 AN: 33460

American (AMR) AF: 0.00127 AC: 57 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00383 AC: 100 AN: 26122

East Asian (EAS) AF: 0.00 AC: 0 AN: 39666

South Asian (SAS) AF: 0.0000464 AC: 4 AN: 86232

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53398

Middle Eastern (MID) AF: 0.00226 AC: 13 AN: 5762

European-Non Finnish (NFE) AF: 0.000156 AC: 173 AN: 1111422

Other (OTH) AF: 0.00123 AC: 74 AN: 60362

GnomAD4 genome AF: 0.00144 AC: 220 AN: 152330 Hom.: 0 Cov.: 33 AF XY: 0.00132 AC XY: 98 AN XY: 74500

African (AFR) AF: 0.00447 AC: 186 AN: 41582

American (AMR) AF: 0.000784 AC: 12 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00231 AC: 8 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000191 AC: 13 AN: 68014

Other (OTH) AF: 0.000473 AC: 1 AN: 2114

Alfa AF: 0.000826 Hom.: 0

Bravo AF: 0.00174

EpiCase AF: 0.000491

EpiControl AF: 0.000178

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	5.1
DANN	Benign	0.76
PhyloP100		-0.046
Mutation Taster		=94/6	polymorphism

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: rs77438668; hg19: chr6-114267287;