6-113956702-G-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

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

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 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 GnomAd at 231 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HDAC2	NM_001527.4	c.284-9C>A		splice_polypyrimidine_tract_variant, intron_variant		ENST00000519065.6
HDAC2	XM_047418692.1	c.194-9C>A		splice_polypyrimidine_tract_variant, intron_variant
HDAC2	NR_033441.2	n.552-9C>A		splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant
HDAC2	NR_073443.2	n.482-9C>A		splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.00152 AC: 231 AN: 152220 Hom.: 0 Cov.: 33

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.: 1 AF XY: 0.00156 AC XY: 209 AN XY: 134218

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.: 10 Cov.: 26 AF XY: 0.00249 AC XY: 1789 AN XY: 719028

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.: 0 Cov.: 33 AF XY: 0.00133 AC XY: 99 AN XY: 74366

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.: 0

Bravo AF: 0.00164

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
Cadd	Benign	20
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

Other links and lift over

dbSNP: rs200805519; hg19: chr6-114277866;