rs2073963

Variant names:

• chr7-18838251-T-G
• rs2073963
• NM_178425.4:c.2684+2254T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_178425.4(HDAC9):​c.2684+2254T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.431 in 151,806 control chromosomes in the GnomAD database, including 14,205 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.43 (14205 hom., cov: 32)
• Consequence: HDAC9 NM_178425.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0870
• Publications: 26 publications found

Genes affected

HDAC9 (HGNC:14065): (histone deacetylase 9) Histones play a critical role in transcriptional regulation, cell cycle progression, and developmental events. Histone acetylation/deacetylation alters chromosome structure and affects transcription factor access to DNA. The protein encoded by this gene has sequence homology to members of the histone deacetylase family. This gene is orthologous to the Xenopus and mouse MITR genes. The MITR protein lacks the histone deacetylase catalytic domain. It represses MEF2 activity through recruitment of multicomponent corepressor complexes that include CtBP and HDACs. This encoded protein may play a role in hematopoiesis. Multiple alternatively spliced transcripts have been described for this gene but the full-length nature of some of them has not been determined. [provided by RefSeq, Jul 2008]

HDAC9 Gene-Disease associations (from GenCC):

• auriculocondylar syndrome 4

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.531 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HDAC9	NM_178425.4	c.2684+2254T>G		intron_variant	Intron 21 of 25	ENST00000686413.1	NP_848512.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HDAC9	ENST00000686413.1	c.2684+2254T>G		intron_variant	Intron 21 of 25		NM_178425.4	ENSP00000509161.1

Frequencies

GnomAD3 genomes AF: 0.431 AC: 65353 AN: 151686 Hom.: 14181 Cov.: 32

Gnomad AFR AF: 0.486

Gnomad AMI AF: 0.534

Gnomad AMR AF: 0.400

Gnomad ASJ AF: 0.398

Gnomad EAS AF: 0.494

Gnomad SAS AF: 0.548

Gnomad FIN AF: 0.417

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.394

Gnomad OTH AF: 0.422

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.431 AC: 65423 AN: 151806 Hom.: 14205 Cov.: 32 AF XY: 0.435 AC XY: 32252 AN XY: 74206

African (AFR) AF: 0.486 AC: 20114 AN: 41408

American (AMR) AF: 0.400 AC: 6085 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.398 AC: 1377 AN: 3464

East Asian (EAS) AF: 0.495 AC: 2549 AN: 5154

South Asian (SAS) AF: 0.549 AC: 2641 AN: 4814

European-Finnish (FIN) AF: 0.417 AC: 4403 AN: 10560

Middle Eastern (MID) AF: 0.425 AC: 125 AN: 294

European-Non Finnish (NFE) AF: 0.394 AC: 26750 AN: 67882

Other (OTH) AF: 0.425 AC: 895 AN: 2104

Alfa AF: 0.404 Hom.: 49871

Bravo AF: 0.429

Asia WGS AF: 0.516 AC: 1793 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.2
DANN	Benign	0.41
PhyloP100		0.087
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
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

Other links and lift over

dbSNP: rs2073963; hg19: chr7-18877874;