rs3744581

Positions:

chr17-11747740-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001372.4(DNAH9):c.6584A>G(p.Asn2195Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.218 in 1,613,082 control chromosomes in the GnomAD database, including 39,777 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.21 ( 3390 hom., cov: 31)

Exomes 𝑓: 0.22 ( 36387 hom. )

Consequence

DNAH9
NM_001372.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 7.48

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0018789768).

BP6

Variant 17-11747740-A-G is Benign according to our data. Variant chr17-11747740-A-G is described in ClinVar as [Benign]. Clinvar id is 402778.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.338 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH9	NM_001372.4 linkuse as main transcript	c.6584A>G	p.Asn2195Ser	missense_variant	32/69	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.6584A>G	p.Asn2195Ser	missense_variant	32/69	1	NM_001372.4	ENSP00000262442	P1	Q9NYC9-1
DNAH9	ENST00000454412.6 linkuse as main transcript	c.6584A>G	p.Asn2195Ser	missense_variant	32/68	5		ENSP00000414874

Frequencies

GnomAD3 genomes

AF:

0.206

AC:

31333

AN:

152014

Hom.:

3383

Cov.:

show subpopulations

Gnomad AFR

AF:

0.160

Gnomad AMI

AF:

0.173

Gnomad AMR

AF:

0.232

Gnomad ASJ

AF:

0.228

Gnomad EAS

AF:

0.351

Gnomad SAS

AF:

0.188

Gnomad FIN

AF:

0.159

Gnomad MID

AF:

0.231

Gnomad NFE

AF:

0.225

Gnomad OTH

AF:

0.224

GnomAD3 exomes

AF:

0.221

AC:

55459

AN:

250952

Hom.:

6448

AF XY:

0.222

AC XY:

30127

AN XY:

135610

show subpopulations

Gnomad AFR exome

AF:

0.159

Gnomad AMR exome

AF:

0.197

Gnomad ASJ exome

AF:

0.235

Gnomad EAS exome

AF:

0.366

Gnomad SAS exome

AF:

0.187

Gnomad FIN exome

AF:

0.161

Gnomad NFE exome

AF:

0.233

Gnomad OTH exome

AF:

0.229

GnomAD4 exome

AF:

0.220

AC:

321009

AN:

1460950

Hom.:

36387

Cov.:

AF XY:

0.219

AC XY:

159378

AN XY:

726786

show subpopulations

Gnomad4 AFR exome

AF:

0.160

Gnomad4 AMR exome

AF:

0.203

Gnomad4 ASJ exome

AF:

0.234

Gnomad4 EAS exome

AF:

0.375

Gnomad4 SAS exome

AF:

0.187

Gnomad4 FIN exome

AF:

0.170

Gnomad4 NFE exome

AF:

0.221

Gnomad4 OTH exome

AF:

0.216

GnomAD4 genome

AF:

0.206

AC:

31354

AN:

152132

Hom.:

3390

Cov.:

AF XY:

0.203

AC XY:

15131

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.160

Gnomad4 AMR

AF:

0.232

Gnomad4 ASJ

AF:

0.228

Gnomad4 EAS

AF:

0.351

Gnomad4 SAS

AF:

0.189

Gnomad4 FIN

AF:

0.159

Gnomad4 NFE

AF:

0.225

Gnomad4 OTH

AF:

0.222

Alfa

AF:

0.231

Hom.:

10087

Bravo

AF:

0.211

TwinsUK

AF:

0.230

AC:

854

ALSPAC

AF:

0.215

AC:

827

ESP6500AA

AF:

0.162

AC:

712

ESP6500EA

AF:

0.244

AC:

2099

ExAC

AF:

0.222

AC:

26902

Asia WGS

AF:

0.261

AC:

909

AN:

3478

EpiCase

AF:

0.240

EpiControl

AF:

0.241

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	This variant is associated with the following publications: (PMID: 17000706) -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

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: Frequency, variant associated with risk of colorectal cancer -

Ciliary dyskinesia, primary, 40

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.30

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.18

T;.

Eigen

Uncertain

0.47

Eigen_PC

Uncertain

0.41

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.89

D;D

MetaRNN

Benign

0.0019

T;T

MetaSVM

Benign

-1.3

MutationAssessor

Uncertain

2.2

M;.

MutationTaster

Benign

0.013

P;P

PrimateAI

Benign

0.44

PROVEAN

Uncertain

-4.1

D;D

REVEL

Uncertain

0.61

Sift

Benign

0.036

D;D

Polyphen

0.87

P;.

Vest4

0.17

MPC

0.20

ClinPred

0.070

GERP RS

3.3

Varity_R

0.24

gMVP

0.20

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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