NM_001527.4:c.1318_1321delAAAG

Variant names:

• chr6-113943407-CCTTT-C
• NM_001527.4:c.1318_1321delAAAG

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001527.4(HDAC2):​c.1318_1321delAAAG​(p.Lys440GlufsTer65) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: HDAC2 NM_001527.4 frameshift
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 7.43
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.1318_1321delAAAG	p.Lys440GlufsTer65	frameshift	Exon 12 of 14	NP_001518.3	Q92769-1
	HDAC2	NR_033441.2		n.1586_1589delAAAG		non_coding_transcript_exon	Exon 13 of 15
	HDAC2	NR_073443.2		n.1516_1519delAAAG		non_coding_transcript_exon	Exon 12 of 14

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HDAC2	ENST00000519065.6	TSL:1 MANE Select	c.1318_1321delAAAG	p.Lys440GlufsTer65	frameshift	Exon 12 of 14	ENSP00000430432.1	Q92769-1
	HDAC2	ENST00000916847.1		c.1357_1360delAAAG	p.Lys453GlufsTer65	frameshift	Exon 12 of 14	ENSP00000586906.1
	HDAC2	ENST00000869750.1		c.1342_1345delAAAG	p.Lys448GlufsTer65	frameshift	Exon 12 of 14	ENSP00000539809.1

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	1	-	HDAC2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.4

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

hg19: chr6-114264571;