17-11640293-A-G

Position:

chr17-11640293-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001372.4(DNAH9):c.1810A>G(p.Met604Val) variant causes a missense change. The variant allele was found at a frequency of 0.0257 in 1,613,072 control chromosomes in the GnomAD database, including 689 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.020 ( 58 hom., cov: 32)

Exomes 𝑓: 0.026 ( 631 hom. )

Consequence

DNAH9
NM_001372.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 4.88

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=0.011774987).

BP6

Variant 17-11640293-A-G is Benign according to our data. Variant chr17-11640293-A-G is described in ClinVar as [Benign]. Clinvar id is 402775.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-11640293-A-G is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0203 (3098/152300) while in subpopulation SAS AF= 0.0304 (147/4828). AF 95% confidence interval is 0.0278. There are 58 homozygotes in gnomad4. There are 1426 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 58 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH9	NM_001372.4 linkuse as main transcript	c.1810A>G	p.Met604Val	missense_variant	10/69	ENST00000262442.9	NP_001363.2	Q9NYC9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAH9	ENST00000262442.9 linkuse as main transcript	c.1810A>G	p.Met604Val	missense_variant	10/69	1	NM_001372.4	ENSP00000262442.3		Q9NYC9-1
DNAH9	ENST00000454412.6 linkuse as main transcript	c.1810A>G	p.Met604Val	missense_variant	10/68	5		ENSP00000414874.2		E7EP17

Frequencies

GnomAD3 genomes

AF:

0.0204

AC:

3099

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00507

Gnomad AMI

AF:

0.0263

Gnomad AMR

AF:

0.0184

Gnomad ASJ

AF:

0.0467

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0302

Gnomad FIN

AF:

0.0219

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0289

Gnomad OTH

AF:

0.0302

GnomAD3 exomes

AF:

0.0232

AC:

5834

AN:

251188

Hom.:

AF XY:

0.0251

AC XY:

3412

AN XY:

135776

show subpopulations

Gnomad AFR exome

AF:

0.00437

Gnomad AMR exome

AF:

0.0108

Gnomad ASJ exome

AF:

0.0440

Gnomad EAS exome

AF:

0.000381

Gnomad SAS exome

AF:

0.0304

Gnomad FIN exome

AF:

0.0226

Gnomad NFE exome

AF:

0.0296

Gnomad OTH exome

AF:

0.0258

GnomAD4 exome

AF:

0.0263

AC:

38398

AN:

1460772

Hom.:

631

Cov.:

AF XY:

0.0269

AC XY:

19568

AN XY:

726748

show subpopulations

Gnomad4 AFR exome

AF:

0.00404

Gnomad4 AMR exome

AF:

0.0117

Gnomad4 ASJ exome

AF:

0.0440

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.0322

Gnomad4 FIN exome

AF:

0.0222

Gnomad4 NFE exome

AF:

0.0278

Gnomad4 OTH exome

AF:

0.0241

GnomAD4 genome

AF:

0.0203

AC:

3098

AN:

152300

Hom.:

Cov.:

AF XY:

0.0192

AC XY:

1426

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.00505

Gnomad4 AMR

AF:

0.0184

Gnomad4 ASJ

AF:

0.0467

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.0304

Gnomad4 FIN

AF:

0.0219

Gnomad4 NFE

AF:

0.0289

Gnomad4 OTH

AF:

0.0294

Alfa

AF:

0.0285

Hom.:

112

Bravo

AF:

0.0196

TwinsUK

AF:

0.0286

AC:

106

ALSPAC

AF:

0.0278

AC:

107

ESP6500AA

AF:

0.00363

AC:

ESP6500EA

AF:

0.0322

AC:

277

ExAC

AF:

0.0236

AC:

2863

Asia WGS

AF:

0.0120

AC:

AN:

3478

EpiCase

AF:

0.0300

EpiControl

AF:

0.0290

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

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: Candidate PCD gene, but frequency is high -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.26

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.096

T;.

Eigen

Uncertain

0.66

Eigen_PC

Uncertain

0.63

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.86

D;D

MetaRNN

Benign

0.012

T;T

MetaSVM

Benign

-0.59

MutationAssessor

Uncertain

2.8

M;.

PrimateAI

Uncertain

0.49

PROVEAN

Uncertain

-3.3

D;D

REVEL

Uncertain

0.38

Sift

Benign

0.033

D;D

Polyphen

0.95

P;.

Vest4

0.13

MPC

0.14

ClinPred

0.026

GERP RS

5.4

Varity_R

0.45

gMVP

0.38

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