Variant chr17-11962145-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001372.4(DNAH9):c.13122G>A(p.Met4374Ile) variant causes a missense change. The variant allele was found at a frequency of 0.182 in 1,613,930 control chromosomes in the GnomAD database, including 27,520 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.17 ( 2395 hom., cov: 32)

Exomes 𝑓: 0.18 ( 25125 hom. )

Consequence

DNAH9
NM_001372.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 6.83

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:

ENSG00000266368 (HGNC:):

ENSG00000266368 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=0.001670748).

BP6

Variant 17-11962145-G-A is Benign according to our data. Variant chr17-11962145-G-A is described in ClinVar as [Benign]. Clinvar id is 402788.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.204 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH9	NM_001372.4 link	c.13122G>A	p.Met4374Ile	missense_variant	68/69	ENST00000262442.9	NP_001363.2	Q9NYC9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAH9	ENST00000262442.9 link	c.13122G>A	p.Met4374Ile	missense_variant	68/69	1	NM_001372.4	ENSP00000262442.3		Q9NYC9-1

Frequencies

GnomAD3 genomes

AF:

0.173

AC:

26329

AN:

151962

Hom.:

2390

Cov.:

show subpopulations

Gnomad AFR

AF:

0.129

Gnomad AMI

AF:

0.310

Gnomad AMR

AF:

0.210

Gnomad ASJ

AF:

0.165

Gnomad EAS

AF:

0.192

Gnomad SAS

AF:

0.145

Gnomad FIN

AF:

0.209

Gnomad MID

AF:

0.191

Gnomad NFE

AF:

0.185

Gnomad OTH

AF:

0.177

GnomAD3 exomes

AF:

0.190

AC:

47605

AN:

250890

Hom.:

4804

AF XY:

0.185

AC XY:

25101

AN XY:

135574

show subpopulations

Gnomad AFR exome

AF:

0.124

Gnomad AMR exome

AF:

0.282

Gnomad ASJ exome

AF:

0.160

Gnomad EAS exome

AF:

0.192

Gnomad SAS exome

AF:

0.142

Gnomad FIN exome

AF:

0.204

Gnomad NFE exome

AF:

0.183

Gnomad OTH exome

AF:

0.193

GnomAD4 exome

AF:

0.183

AC:

267642

AN:

1461850

Hom.:

25125

Cov.:

AF XY:

0.181

AC XY:

131611

AN XY:

727230

show subpopulations

Gnomad4 AFR exome

AF:

0.123

Gnomad4 AMR exome

AF:

0.270

Gnomad4 ASJ exome

AF:

0.162

Gnomad4 EAS exome

AF:

0.181

Gnomad4 SAS exome

AF:

0.144

Gnomad4 FIN exome

AF:

0.205

Gnomad4 NFE exome

AF:

0.184

Gnomad4 OTH exome

AF:

0.181

GnomAD4 genome

AF:

0.173

AC:

26356

AN:

152080

Hom.:

2395

Cov.:

AF XY:

0.173

AC XY:

12895

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.129

Gnomad4 AMR

AF:

0.210

Gnomad4 ASJ

AF:

0.165

Gnomad4 EAS

AF:

0.191

Gnomad4 SAS

AF:

0.145

Gnomad4 FIN

AF:

0.209

Gnomad4 NFE

AF:

0.185

Gnomad4 OTH

AF:

0.178

Alfa

AF:

0.183

Hom.:

6450

Bravo

AF:

0.176

TwinsUK

AF:

0.196

AC:

727

ALSPAC

AF:

0.187

AC:

719

ESP6500AA

AF:

0.126

AC:

555

ESP6500EA

AF:

0.179

AC:

1538

ExAC

AF:

0.184

AC:

22337

Asia WGS

AF:

0.156

AC:

542

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -
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: Frequency -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.61

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.53

CADD

Uncertain

DANN

Benign

0.97

DEOGEN2

Benign

0.064

T;.;.

Eigen

Uncertain

0.29

Eigen_PC

Uncertain

0.39

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.75

T;T;T

MetaRNN

Benign

0.0017

T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

1.5

L;.;.

PrimateAI

Uncertain

0.55

PROVEAN

Uncertain

-3.4

D;D;.

REVEL

Benign

0.15

Sift

Uncertain

0.021

D;D;.

Sift4G

Uncertain

0.032

.;.;D

Polyphen

0.35

B;.;.

Vest4

0.21

MutPred

0.61

Loss of disorder (P = 0.0837);.;.;

MPC

0.15

ClinPred

0.018

GERP RS

4.0

Varity_R

0.62

gMVP

0.41

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