NM_001372.4:c.11407-2575C>T

Variant names:

• chr17-11900144-C-T
• rs4792192
• NM_001372.4:c.11407-2575C>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.11407-2575C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.734 in 151,218 control chromosomes in the GnomAD database, including 44,004 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 0.73 (44004 hom., cov: 28)
• Consequence: DNAH9 NM_001372.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.427
• Publications: 6 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: Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen, G2P
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.882 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.11407-2575C>T		intron	N/A	NP_001363.2	Q9NYC9-1
	DNAH9	NM_004662.2		c.343-2575C>T		intron	N/A	NP_004653.2	Q99499

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH9	ENST00000262442.9	TSL:1 MANE Select	c.11407-2575C>T		intron	N/A	ENSP00000262442.3	Q9NYC9-1
	DNAH9	ENST00000608377.5	TSL:1	c.343-2575C>T		intron	N/A	ENSP00000476951.1	Q9NYC9-3
	DNAH9	ENST00000396001.6	TSL:1	n.870-2575C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.734 AC: 110919 AN: 151100 Hom.: 43994 Cov.: 28

Gnomad AFR AF: 0.409

Gnomad AMI AF: 0.873

Gnomad AMR AF: 0.812

Gnomad ASJ AF: 0.841

Gnomad EAS AF: 0.645

Gnomad SAS AF: 0.813

Gnomad FIN AF: 0.854

Gnomad MID AF: 0.854

Gnomad NFE AF: 0.887

Gnomad OTH AF: 0.776

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

GnomAD4 genome AF: 0.734 AC: 110953 AN: 151218 Hom.: 44004 Cov.: 28 AF XY: 0.734 AC XY: 54175 AN XY: 73778

African (AFR) AF: 0.409 AC: 16849 AN: 41230

American (AMR) AF: 0.812 AC: 12360 AN: 15214

Ashkenazi Jewish (ASJ) AF: 0.841 AC: 2915 AN: 3468

East Asian (EAS) AF: 0.647 AC: 3299 AN: 5102

South Asian (SAS) AF: 0.812 AC: 3877 AN: 4772

European-Finnish (FIN) AF: 0.854 AC: 8766 AN: 10270

Middle Eastern (MID) AF: 0.854 AC: 251 AN: 294

European-Non Finnish (NFE) AF: 0.887 AC: 60212 AN: 67846

Other (OTH) AF: 0.772 AC: 1628 AN: 2110

Alfa AF: 0.812 Hom.: 110743

Bravo AF: 0.715

Asia WGS AF: 0.694 AC: 2410 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.23
DANN	Benign	0.46
PhyloP100		-0.43
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: rs4792192; hg19: chr17-11803461;