17-11608140-C-T

Variant names:

• chr17-11608140-C-T
• rs11078022
• NM_001372.4:c.429C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001372.4(DNAH9):​c.429C>T​(p.Pro143Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.418 in 1,594,930 control chromosomes in the GnomAD database, including 145,822 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.37 (11811 hom., cov: 33)
  • Exomes 𝑓: 0.42 (134011 hom.)
• Consequence: DNAH9 NM_001372.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -1.63
• Publications: 21 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 17-11608140-C-T is Benign according to our data. Variant chr17-11608140-C-T is described in ClinVar as Benign. ClinVar VariationId is 402773.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.601 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.429C>T	p.Pro143Pro	synonymous	Exon 2 of 69	NP_001363.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH9	ENST00000262442.9	TSL:1 MANE Select	c.429C>T	p.Pro143Pro	synonymous	Exon 2 of 69	ENSP00000262442.3
	DNAH9	ENST00000579406.1	TSL:1	n.456C>T		non_coding_transcript_exon	Exon 2 of 8
	DNAH9	ENST00000454412.6	TSL:5	c.429C>T	p.Pro143Pro	synonymous	Exon 2 of 68	ENSP00000414874.2

Frequencies

GnomAD3 genomes AF: 0.373 AC: 56743 AN: 152006 Hom.: 11802 Cov.: 33

Gnomad AFR AF: 0.203

Gnomad AMI AF: 0.344

Gnomad AMR AF: 0.525

Gnomad ASJ AF: 0.479

Gnomad EAS AF: 0.549

Gnomad SAS AF: 0.620

Gnomad FIN AF: 0.382

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.403

Gnomad OTH AF: 0.422

GnomAD2 exomes AF: 0.459 AC: 113315 AN: 246682 AF XY: 0.463

Gnomad AFR exome AF: 0.197

Gnomad AMR exome AF: 0.633

Gnomad ASJ exome AF: 0.480

Gnomad EAS exome AF: 0.542

Gnomad FIN exome AF: 0.379

Gnomad NFE exome AF: 0.406

Gnomad OTH exome AF: 0.454

GnomAD4 exome AF: 0.422 AC: 609338 AN: 1442806 Hom.: 134011 Cov.: 34 AF XY: 0.427 AC XY: 304922 AN XY: 714354

African (AFR) AF: 0.191 AC: 6294 AN: 33028

American (AMR) AF: 0.624 AC: 27100 AN: 43422

Ashkenazi Jewish (ASJ) AF: 0.479 AC: 12328 AN: 25722

East Asian (EAS) AF: 0.584 AC: 22861 AN: 39162

South Asian (SAS) AF: 0.603 AC: 51174 AN: 84870

European-Finnish (FIN) AF: 0.377 AC: 20040 AN: 53192

Middle Eastern (MID) AF: 0.511 AC: 2911 AN: 5696

European-Non Finnish (NFE) AF: 0.402 AC: 440955 AN: 1098204

Other (OTH) AF: 0.431 AC: 25675 AN: 59510

GnomAD4 genome AF: 0.373 AC: 56771 AN: 152124 Hom.: 11811 Cov.: 33 AF XY: 0.380 AC XY: 28287 AN XY: 74360

African (AFR) AF: 0.203 AC: 8435 AN: 41496

American (AMR) AF: 0.526 AC: 8032 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.479 AC: 1662 AN: 3472

East Asian (EAS) AF: 0.549 AC: 2840 AN: 5174

South Asian (SAS) AF: 0.619 AC: 2991 AN: 4830

European-Finnish (FIN) AF: 0.382 AC: 4034 AN: 10564

Middle Eastern (MID) AF: 0.531 AC: 156 AN: 294

European-Non Finnish (NFE) AF: 0.403 AC: 27413 AN: 67990

Other (OTH) AF: 0.423 AC: 894 AN: 2112

Alfa AF: 0.397 Hom.: 51909

Bravo AF: 0.372

Asia WGS AF: 0.559 AC: 1943 AN: 3478

EpiCase AF: 0.417

EpiControl AF: 0.420

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	Ciliary dyskinesia, primary, 40 (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.64
DANN	Benign	0.47
PhyloP100		-1.6
Mutation Taster		=97/3	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: rs11078022; hg19: chr17-11511457; COSMIC: COSV52339774; COSMIC: COSV52339774;