rs2322047

Variant names:

• chr17-11712470-A-G
• rs2322047
• NM_001372.4:c.5553-6864A>G

Variant summary

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

The NM_001372.4(DNAH9):​c.5553-6864A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.83 in 151,902 control chromosomes in the GnomAD database, including 55,993 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 0.83 (55993 hom., cov: 30)
• Consequence: DNAH9 NM_001372.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.302
• Publications: 3 publications found

Genes affected

DNAH9 (HGNC:2953): (dynein axonemal heavy chain 9) This gene encodes the heavy chain subunit of axonemal dynein, a large multi-subunit molecular motor. Axonemal dynein attaches to microtubules and hydrolyzes ATP to mediate the movement of cilia and flagella. The gene expresses at least two transcript variants; additional variants have been described, but their full length nature has not been determined. [provided by RefSeq, Jul 2008]

DNAH9 Gene-Disease associations (from GenCC):

• ciliary dyskinesia, primary, 40

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics, PanelApp Australia
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• situs inversus

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• schizophrenia

  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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001372.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH9	NM_001372.4	MANE Select	c.5553-6864A>G		intron	N/A	NP_001363.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH9	ENST00000262442.9	TSL:1 MANE Select	c.5553-6864A>G		intron	N/A	ENSP00000262442.3
	DNAH9	ENST00000454412.6	TSL:5	c.5553-6864A>G		intron	N/A	ENSP00000414874.2

Frequencies

GnomAD3 genomes AF: 0.831 AC: 126075 AN: 151784 Hom.: 55982 Cov.: 30

Gnomad AFR AF: 0.480

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.916

Gnomad ASJ AF: 0.952

Gnomad EAS AF: 0.875

Gnomad SAS AF: 0.844

Gnomad FIN AF: 0.998

Gnomad MID AF: 0.934

Gnomad NFE AF: 0.983

Gnomad OTH AF: 0.872

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

GnomAD4 genome AF: 0.830 AC: 126112 AN: 151902 Hom.: 55993 Cov.: 30 AF XY: 0.834 AC XY: 61876 AN XY: 74232

African (AFR) AF: 0.479 AC: 19807 AN: 41336

American (AMR) AF: 0.916 AC: 13977 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.952 AC: 3304 AN: 3470

East Asian (EAS) AF: 0.875 AC: 4503 AN: 5144

South Asian (SAS) AF: 0.846 AC: 4078 AN: 4820

European-Finnish (FIN) AF: 0.998 AC: 10571 AN: 10590

Middle Eastern (MID) AF: 0.935 AC: 275 AN: 294

European-Non Finnish (NFE) AF: 0.983 AC: 66852 AN: 67976

Other (OTH) AF: 0.871 AC: 1835 AN: 2106

Alfa AF: 0.932 Hom.: 27275

Bravo AF: 0.808

Asia WGS AF: 0.819 AC: 2851 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.9
DANN	Benign	0.75
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: rs2322047; hg19: chr17-11615787;