Variant chr6-113956702-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001527.4(HDAC2):c.284-9C>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00247 in 1,595,070 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0015 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0026 ( 10 hom. )

Consequence

HDAC2
NM_001527.4 splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.009774

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.537

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 Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.59).

BP6

Variant 6-113956702-G-T is Benign according to our data. Variant chr6-113956702-G-T is described in ClinVar as [Benign]. Clinvar id is 735937.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr6-113956702-G-T is described in Lovd as [Likely_benign].

BS2

High AC in GnomAd4 at 231 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
HDAC2	NM_001527.4 linkuse as main transcript	c.284-9C>A	splice_polypyrimidine_tract_variant, intron_variant	ENST00000519065.6	NP_001518.3
HDAC2	XM_047418692.1 linkuse as main transcript	c.194-9C>A	splice_polypyrimidine_tract_variant, intron_variant		XP_047274648.1
HDAC2	NR_033441.2 linkuse as main transcript	n.552-9C>A	splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant
HDAC2	NR_073443.2 linkuse as main transcript	n.482-9C>A	splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HDAC2	ENST00000519065.6 linkuse as main transcript	c.284-9C>A		splice_polypyrimidine_tract_variant, intron_variant		1	NM_001527.4	ENSP00000430432	P1	Q92769-1

Frequencies

GnomAD3 genomes

AF:

0.00152

AC:

231

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000941

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00256

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00145

AC:

358

AN:

247248

Hom.:

AF XY:

0.00156

AC XY:

209

AN XY:

134218

show subpopulations

Gnomad AFR exome

AF:

0.000982

Gnomad AMR exome

AF:

0.000586

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000165

Gnomad FIN exome

AF:

0.000372

Gnomad NFE exome

AF:

0.00270

Gnomad OTH exome

AF:

0.00117

GnomAD4 exome

AF:

0.00257

AC:

3711

AN:

1442850

Hom.:

Cov.:

AF XY:

0.00249

AC XY:

1789

AN XY:

719028

show subpopulations

Gnomad4 AFR exome

AF:

0.000363

Gnomad4 AMR exome

AF:

0.000630

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000105

Gnomad4 FIN exome

AF:

0.000581

Gnomad4 NFE exome

AF:

0.00320

Gnomad4 OTH exome

AF:

0.00214

GnomAD4 genome

AF:

0.00152

AC:

231

AN:

152220

Hom.:

Cov.:

AF XY:

0.00133

AC XY:

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.000941

Gnomad4 AMR

AF:

0.000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.00256

Gnomad4 OTH

AF:

0.00239

Alfa

AF:

0.00209

Hom.:

Bravo

AF:

0.00164

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Benign

0.84

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0098

dbscSNV1_RF

Benign

0.12

SpliceAI score (max)

0.16

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over