NM_001372.4:c.8420+1783G>T

Variant names:

• chr17-11799576-G-T
• rs11650055
• NM_001372.4:c.8420+1783G>T

Variant summary

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

The NM_001372.4(DNAH9):​c.8420+1783G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.436 in 151,340 control chromosomes in the GnomAD database, including 14,769 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 0.44 (14769 hom., cov: 30)
• Consequence: DNAH9 NM_001372.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.92
• Publications: 2 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=-1.02).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.49 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH9	NM_001372.4	MANE Select	c.8420+1783G>T		intron	N/A	NP_001363.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH9	ENST00000262442.9	TSL:1 MANE Select	c.8420+1783G>T		intron	N/A	ENSP00000262442.3
	DNAH9	ENST00000454412.6	TSL:5	c.8420+1783G>T		intron	N/A	ENSP00000414874.2

Frequencies

GnomAD3 genomes AF: 0.436 AC: 65939 AN: 151222 Hom.: 14764 Cov.: 30

Gnomad AFR AF: 0.340

Gnomad AMI AF: 0.391

Gnomad AMR AF: 0.450

Gnomad ASJ AF: 0.464

Gnomad EAS AF: 0.449

Gnomad SAS AF: 0.342

Gnomad FIN AF: 0.447

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.494

Gnomad OTH AF: 0.444

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

GnomAD4 genome AF: 0.436 AC: 65973 AN: 151340 Hom.: 14769 Cov.: 30 AF XY: 0.433 AC XY: 32041 AN XY: 73940

African (AFR) AF: 0.340 AC: 13999 AN: 41220

American (AMR) AF: 0.450 AC: 6841 AN: 15200

Ashkenazi Jewish (ASJ) AF: 0.464 AC: 1606 AN: 3464

East Asian (EAS) AF: 0.448 AC: 2295 AN: 5118

South Asian (SAS) AF: 0.344 AC: 1646 AN: 4790

European-Finnish (FIN) AF: 0.447 AC: 4673 AN: 10444

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.494 AC: 33519 AN: 67808

Other (OTH) AF: 0.444 AC: 929 AN: 2092

Alfa AF: 0.387 Hom.: 1736

Bravo AF: 0.430

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.28
DANN	Benign	0.51
PhyloP100		-2.9
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: rs11650055; hg19: chr17-11702893;