rs10521191

Variant names:

• chr17-11816440-T-C
• rs10521191
• NM_001372.4:c.8708-5480T>C

Variant summary

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

The NM_001372.4(DNAH9):​c.8708-5480T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 152,264 control chromosomes in the GnomAD database, including 2,043 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 0.10 (2043 hom., cov: 33)
• Consequence: DNAH9 NM_001372.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.911
• Publications: 1 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 (AFR) allele frequency at 95% confidence interval = 0.299 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH9	NM_001372.4	c.8708-5480T>C		intron_variant	Intron 45 of 68	ENST00000262442.9	NP_001363.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH9	ENST00000262442.9	c.8708-5480T>C		intron_variant	Intron 45 of 68	1	NM_001372.4	ENSP00000262442.3
DNAH9	ENST00000454412.6	c.8708-5480T>C		intron_variant	Intron 45 of 67	5		ENSP00000414874.2

Frequencies

GnomAD3 genomes AF: 0.100 AC: 15276 AN: 152146 Hom.: 2026 Cov.: 33

Gnomad AFR AF: 0.303

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0570

Gnomad ASJ AF: 0.0121

Gnomad EAS AF: 0.175

Gnomad SAS AF: 0.0717

Gnomad FIN AF: 0.00819

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00489

Gnomad OTH AF: 0.0689

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

GnomAD4 genome AF: 0.101 AC: 15344 AN: 152264 Hom.: 2043 Cov.: 33 AF XY: 0.0997 AC XY: 7427 AN XY: 74460

African (AFR) AF: 0.304 AC: 12610 AN: 41514

American (AMR) AF: 0.0568 AC: 870 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.0121 AC: 42 AN: 3472

East Asian (EAS) AF: 0.174 AC: 901 AN: 5168

South Asian (SAS) AF: 0.0715 AC: 345 AN: 4822

European-Finnish (FIN) AF: 0.00819 AC: 87 AN: 10620

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.00491 AC: 334 AN: 68040

Other (OTH) AF: 0.0710 AC: 150 AN: 2112

Alfa AF: 0.0650 Hom.: 168

Bravo AF: 0.112

Asia WGS AF: 0.138 AC: 479 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.67
DANN	Benign	0.50
PhyloP100		-0.91
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: rs10521191; hg19: chr17-11719757;