rs117483481

Positions:

chr17-11854038-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001372.4(DNAH9):c.9543G>A(p.Pro3181=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00415 in 1,614,032 control chromosomes in the GnomAD database, including 48 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0037 ( 3 hom., cov: 31)

Exomes 𝑓: 0.0042 ( 45 hom. )

Consequence

DNAH9
NM_001372.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -5.31

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 17-11854038-G-A is Benign according to our data. Variant chr17-11854038-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 402781.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-5.31 with no splicing effect.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00368 (560/152192) while in subpopulation EAS AF= 0.0321 (166/5170). AF 95% confidence interval is 0.0281. There are 3 homozygotes in gnomad4. There are 263 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH9	NM_001372.4 linkuse as main transcript	c.9543G>A	p.Pro3181=	synonymous_variant	50/69	ENST00000262442.9	NP_001363.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAH9	ENST00000262442.9 linkuse as main transcript	c.9543G>A	p.Pro3181=	synonymous_variant	50/69	1	NM_001372.4	ENSP00000262442	P1	Q9NYC9-1
DNAH9	ENST00000454412.6 linkuse as main transcript	c.9543G>A	p.Pro3181=	synonymous_variant	50/68	5		ENSP00000414874
DNAH9	ENST00000578834.1 linkuse as main transcript	n.90G>A		non_coding_transcript_exon_variant	2/3	4
DNAH9	ENST00000579703.1 linkuse as main transcript			upstream_gene_variant		3		ENSP00000463622

Frequencies

GnomAD3 genomes

AF:

0.00369

AC:

561

AN:

152074

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00101

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00223

Gnomad ASJ

AF:

0.0101

Gnomad EAS

AF:

0.0320

Gnomad SAS

AF:

0.00644

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00362

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00589

AC:

1479

AN:

251242

Hom.:

AF XY:

0.00585

AC XY:

794

AN XY:

135816

show subpopulations

Gnomad AFR exome

AF:

0.00142

Gnomad AMR exome

AF:

0.00147

Gnomad ASJ exome

AF:

0.0124

Gnomad EAS exome

AF:

0.0370

Gnomad SAS exome

AF:

0.00536

Gnomad FIN exome

AF:

0.0000463

Gnomad NFE exome

AF:

0.00356

Gnomad OTH exome

AF:

0.00473

GnomAD4 exome

AF:

0.00420

AC:

6139

AN:

1461840

Hom.:

Cov.:

AF XY:

0.00427

AC XY:

3103

AN XY:

727220

show subpopulations

Gnomad4 AFR exome

AF:

0.000896

Gnomad4 AMR exome

AF:

0.00174

Gnomad4 ASJ exome

AF:

0.0108

Gnomad4 EAS exome

AF:

0.0225

Gnomad4 SAS exome

AF:

0.00589

Gnomad4 FIN exome

AF:

0.000206

Gnomad4 NFE exome

AF:

0.00352

Gnomad4 OTH exome

AF:

0.00604

GnomAD4 genome

AF:

0.00368

AC:

560

AN:

152192

Hom.:

Cov.:

AF XY:

0.00353

AC XY:

263

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.00101

Gnomad4 AMR

AF:

0.00223

Gnomad4 ASJ

AF:

0.0101

Gnomad4 EAS

AF:

0.0321

Gnomad4 SAS

AF:

0.00624

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.00362

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00376

Hom.:

Bravo

AF:

0.00365

Asia WGS

AF:

0.00837

AC:

AN:

3478

EpiCase

AF:

0.00376

EpiControl

AF:

0.00462

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Candidate PCD gene, but frequency is high -

DNAH9-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 27, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Ciliary dyskinesia, primary, 40

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Nov 08, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.18

DANN

Benign

0.81

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over