Genetic Variant NM_001527.4:c.1172A>C (chr6-113944330-T-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001527.4(HDAC2):c.1172A>C(p.His391Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,812 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

HDAC2
NM_001527.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.85

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.093934864).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HDAC2	NM_001527.4 link	c.1172A>C	p.His391Pro	missense_variant	Exon 11 of 14	ENST00000519065.6	NP_001518.3	Q92769-1
HDAC2	XM_047418692.1 link	c.1082A>C	p.His361Pro	missense_variant	Exon 11 of 14		XP_047274648.1
HDAC2	NR_033441.2 link	n.1440A>C		non_coding_transcript_exon_variant	Exon 12 of 15
HDAC2	NR_073443.2 link	n.1370A>C		non_coding_transcript_exon_variant	Exon 11 of 14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
HDAC2	ENST00000519065.6 link	c.1172A>C	p.His391Pro	missense_variant	Exon 11 of 14	1	NM_001527.4	ENSP00000430432.1	Q92769-1
HDAC2	ENST00000368632.6 link	c.1082A>C	p.His361Pro	missense_variant	Exon 12 of 15	2		ENSP00000357621.2	Q92769-3
HDAC2	ENST00000519108.5 link	c.1082A>C	p.His361Pro	missense_variant	Exon 11 of 14	2		ENSP00000430008.1	Q92769-3
HDAC2	ENST00000523334.1 link	n.4175A>C		non_coding_transcript_exon_variant	Exon 5 of 8	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460812

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726812

show subpopulations

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:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.059

BayesDel_addAF

Benign

-0.091

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Benign

0.90

DEOGEN2

Benign

0.25

T;.;.

Eigen

Benign

-0.35

Eigen_PC

Benign

-0.033

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.85

D;.;D

M_CAP

Benign

0.0096

MetaRNN

Benign

0.094

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.9

N;.;.

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-0.45

N;N;N

REVEL

Benign

0.15

Sift

Benign

0.32

T;T;T

Sift4G

Benign

0.36

T;T;T

Polyphen

0.0

B;.;.

Vest4

0.22

MutPred

0.26

Gain of loop (P = 0.0502);.;.;

MVP

0.43

MPC

0.63

ClinPred

0.39

GERP RS

6.1

Varity_R

0.17

gMVP

0.23

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over