6-113948991-G-T

Variant names:

• chr6-113948991-G-T
• NM_001527.4:c.829C>A

Variant summary

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

The NM_001527.4(HDAC2):​c.829C>A​(p.Leu277Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,558 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: HDAC2 NM_001527.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.56

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 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HDAC2	NM_001527.4	c.829C>A	p.Leu277Ile	missense_variant	Exon 8 of 14	ENST00000519065.6	NP_001518.3
HDAC2	XM_047418692.1	c.739C>A	p.Leu247Ile	missense_variant	Exon 8 of 14		XP_047274648.1
HDAC2	NR_033441.2	n.1097C>A		non_coding_transcript_exon_variant	Exon 9 of 15
HDAC2	NR_073443.2	n.1027C>A		non_coding_transcript_exon_variant	Exon 8 of 14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HDAC2	ENST00000519065.6	c.829C>A	p.Leu277Ile	missense_variant	Exon 8 of 14	1	NM_001527.4	ENSP00000430432.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461558 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727062

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.39
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.040
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.54	D;.;.
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.96	D;.;D
M_CAP	Uncertain	0.14	D
MetaRNN	Uncertain	0.66	D;D;D
MetaSVM	Uncertain	0.071	D
MutationAssessor	Pathogenic	3.2	M;.;.
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-1.8	N;N;N
REVEL	Uncertain	0.61
Sift	Uncertain	0.0010	D;D;D
Sift4G	Uncertain	0.015	D;D;D
Polyphen		0.084	B;.;.
Vest4		0.60
MutPred		0.77		Gain of methylation at K280 (P = 0.0562);.;.;
MVP		0.90
MPC		2.1
ClinPred		0.92	D
GERP RS		3.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.73
gMVP		0.89

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr6-114270155; COSMIC: COSV64038704; COSMIC: COSV64038704;