6-113956005-T-C

Variant names:

• chr6-113956005-T-C
• NM_001527.4:c.497+8A>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001527.4(HDAC2):​c.497+8A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000014 in 1,430,004 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: HDAC2 NM_001527.4 splice_region, intron
• Scores: Splicing: ADA: 0.00001924
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.88

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21524388).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HDAC2	NM_001527.4	c.497+8A>G		splice_region_variant, intron_variant	Intron 5 of 13	ENST00000519065.6	NP_001518.3
HDAC2	XM_047418692.1	c.407+8A>G		splice_region_variant, intron_variant	Intron 5 of 13		XP_047274648.1
HDAC2	NR_033441.2	n.765+8A>G		splice_region_variant, intron_variant	Intron 6 of 14
HDAC2	NR_073443.2	n.695+8A>G		splice_region_variant, intron_variant	Intron 5 of 13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HDAC2	ENST00000519065.6	c.497+8A>G		splice_region_variant, intron_variant	Intron 5 of 13	1	NM_001527.4	ENSP00000430432.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000140 AC: 2 AN: 1430004 Hom.: 0 Cov.: 27 AF XY: 0.00000140 AC XY: 1 AN XY: 711816

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000244

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	1.1
DANN	Uncertain	0.99
Eigen	Benign	0.11
Eigen_PC	Benign	-0.27
FATHMM_MKL	Benign	0.061	N
LIST_S2	Benign	0.18	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.99	T
PROVEAN	Benign	1.2	N
REVEL	Benign	0.048
Sift	Pathogenic	0.0	D
Sift4G	Benign	1.0	T
MutPred		0.60		Loss of methylation at K156 (P = 0.0719);
MVP		0.37
ClinPred		0.055	T
GERP RS		-0.75

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000019
dbscSNV1_RF	Benign	0.020
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-114277169;