rs2249817

Variant names:

• chr7-18856388-A-G
• rs2249817
• NM_178425.4:c.2685-18090A>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.2685-18090A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.566 in 151,944 control chromosomes in the GnomAD database, including 26,046 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 0.57 (26046 hom., cov: 31)
• Consequence: HDAC9 NM_178425.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.299
• Publications: 12 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.778 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178425.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HDAC9	NM_178425.4	MANE Select	c.2685-18090A>G		intron	N/A	NP_848512.1	Q9UKV0-7
	HDAC9	NM_178423.3		c.2676-18090A>G		intron	N/A	NP_848510.1	Q9UKV0-5
	HDAC9	NM_001321868.2		c.2610-18090A>G		intron	N/A	NP_001308797.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HDAC9	ENST00000686413.1	MANE Select	c.2685-18090A>G		intron	N/A	ENSP00000509161.1	Q9UKV0-7
	HDAC9	ENST00000441542.7	TSL:1	c.2685-18090A>G		intron	N/A	ENSP00000408617.2	Q9UKV0-7
	HDAC9	ENST00000406451.8	TSL:1	c.2676-18090A>G		intron	N/A	ENSP00000384657.3	Q9UKV0-5

Frequencies

GnomAD3 genomes AF: 0.566 AC: 85952 AN: 151826 Hom.: 26010 Cov.: 31

Gnomad AFR AF: 0.785

Gnomad AMI AF: 0.532

Gnomad AMR AF: 0.540

Gnomad ASJ AF: 0.528

Gnomad EAS AF: 0.657

Gnomad SAS AF: 0.690

Gnomad FIN AF: 0.444

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.444

Gnomad OTH AF: 0.561

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

GnomAD4 genome AF: 0.566 AC: 86045 AN: 151944 Hom.: 26046 Cov.: 31 AF XY: 0.569 AC XY: 42196 AN XY: 74222

African (AFR) AF: 0.785 AC: 32568 AN: 41482

American (AMR) AF: 0.540 AC: 8225 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.528 AC: 1833 AN: 3470

East Asian (EAS) AF: 0.657 AC: 3392 AN: 5162

South Asian (SAS) AF: 0.689 AC: 3322 AN: 4818

European-Finnish (FIN) AF: 0.444 AC: 4692 AN: 10560

Middle Eastern (MID) AF: 0.646 AC: 190 AN: 294

European-Non Finnish (NFE) AF: 0.444 AC: 30156 AN: 67902

Other (OTH) AF: 0.561 AC: 1183 AN: 2110

Alfa AF: 0.494 Hom.: 37777

Bravo AF: 0.579

Asia WGS AF: 0.685 AC: 2379 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	9.4
DANN	Benign	0.81
PhyloP100		0.30
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: rs2249817; hg19: chr7-18896011;