17-11872043-C-T

Variant names:

• chr17-11872043-C-T
• rs2240519
• NM_001372.4:c.10242+257C>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.10242+257C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.471 in 151,904 control chromosomes in the GnomAD database, including 17,431 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 0.47 (17431 hom., cov: 31)
• Consequence: DNAH9 NM_001372.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.100
• 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: 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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.533 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.10242+257C>T		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.10242+257C>T		intron	N/A	ENSP00000262442.3
	DNAH9	ENST00000454412.6	TSL:5	c.10242+257C>T		intron	N/A	ENSP00000414874.2
	DNAH9	ENST00000579703.1	TSL:3	c.495+2790C>T		intron	N/A	ENSP00000463622.2

Frequencies

GnomAD3 genomes AF: 0.471 AC: 71550 AN: 151786 Hom.: 17423 Cov.: 31

Gnomad AFR AF: 0.400

Gnomad AMI AF: 0.613

Gnomad AMR AF: 0.371

Gnomad ASJ AF: 0.550

Gnomad EAS AF: 0.290

Gnomad SAS AF: 0.415

Gnomad FIN AF: 0.544

Gnomad MID AF: 0.510

Gnomad NFE AF: 0.538

Gnomad OTH AF: 0.466

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

GnomAD4 genome AF: 0.471 AC: 71578 AN: 151904 Hom.: 17431 Cov.: 31 AF XY: 0.470 AC XY: 34874 AN XY: 74204

African (AFR) AF: 0.400 AC: 16585 AN: 41454

American (AMR) AF: 0.370 AC: 5645 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.550 AC: 1910 AN: 3472

East Asian (EAS) AF: 0.290 AC: 1492 AN: 5140

South Asian (SAS) AF: 0.414 AC: 1990 AN: 4806

European-Finnish (FIN) AF: 0.544 AC: 5737 AN: 10554

Middle Eastern (MID) AF: 0.490 AC: 143 AN: 292

European-Non Finnish (NFE) AF: 0.538 AC: 36533 AN: 67928

Other (OTH) AF: 0.467 AC: 986 AN: 2110

Alfa AF: 0.505 Hom.: 13512

Bravo AF: 0.456

Asia WGS AF: 0.365 AC: 1272 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	8.8
DANN	Benign	0.77
PhyloP100		0.10
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: rs2240519; hg19: chr17-11775360;