rs17612861

Positions:

chr17-11932014-G-A

Variant summary

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

The NM_001372.4(DNAH9):c.12106G>A(p.Asp4036Asn) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.304 in 1,613,426 control chromosomes in the GnomAD database, including 77,786 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.25 ( 5493 hom., cov: 32)

Exomes 𝑓: 0.31 ( 72293 hom. )

Consequence

DNAH9
NM_001372.4 missense, splice_region

Scores

Splicing: ADA: 0.2767

Clinical Significance

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

Conservation

PhyloP100: 5.79

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=0.0017387867).

BP6

Variant 17-11932014-G-A is Benign according to our data. Variant chr17-11932014-G-A is described in ClinVar as [Benign]. Clinvar id is 402787.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.328 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH9	NM_001372.4 linkuse as main transcript	c.12106G>A	p.Asp4036Asn	missense_variant, splice_region_variant	64/69	ENST00000262442.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH9	ENST00000262442.9 linkuse as main transcript	c.12106G>A	p.Asp4036Asn	missense_variant, splice_region_variant	64/69	1	NM_001372.4	P1	Q9NYC9-1
DNAH9	ENST00000608377.5 linkuse as main transcript	c.1042G>A	p.Asp348Asn	missense_variant, splice_region_variant	10/15	1			Q9NYC9-3
DNAH9	ENST00000396001.6 linkuse as main transcript	n.1569G>A		splice_region_variant, non_coding_transcript_exon_variant	10/15	1
DNAH9	ENST00000454412.6 linkuse as main transcript	c.11878G>A	p.Asp3960Asn	missense_variant, splice_region_variant	63/68	5

Frequencies

GnomAD3 genomes

AF:

0.247

AC:

37511

AN:

151926

Hom.:

5493

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0762

Gnomad AMI

AF:

0.255

Gnomad AMR

AF:

0.250

Gnomad ASJ

AF:

0.351

Gnomad EAS

AF:

0.194

Gnomad SAS

AF:

0.317

Gnomad FIN

AF:

0.318

Gnomad MID

AF:

0.331

Gnomad NFE

AF:

0.331

Gnomad OTH

AF:

0.286

GnomAD3 exomes

AF:

0.284

AC:

71286

AN:

251116

Hom.:

11065

AF XY:

0.293

AC XY:

39778

AN XY:

135730

show subpopulations

Gnomad AFR exome

AF:

0.0713

Gnomad AMR exome

AF:

0.199

Gnomad ASJ exome

AF:

0.361

Gnomad EAS exome

AF:

0.203

Gnomad SAS exome

AF:

0.305

Gnomad FIN exome

AF:

0.319

Gnomad NFE exome

AF:

0.332

Gnomad OTH exome

AF:

0.317

GnomAD4 exome

AF:

0.309

AC:

452194

AN:

1461382

Hom.:

72293

Cov.:

AF XY:

0.312

AC XY:

226785

AN XY:

726968

show subpopulations

Gnomad4 AFR exome

AF:

0.0628

Gnomad4 AMR exome

AF:

0.208

Gnomad4 ASJ exome

AF:

0.355

Gnomad4 EAS exome

AF:

0.165

Gnomad4 SAS exome

AF:

0.313

Gnomad4 FIN exome

AF:

0.319

Gnomad4 NFE exome

AF:

0.325

Gnomad4 OTH exome

AF:

0.301

GnomAD4 genome

AF:

0.247

AC:

37503

AN:

152044

Hom.:

5493

Cov.:

AF XY:

0.247

AC XY:

18366

AN XY:

74308

show subpopulations

Gnomad4 AFR

AF:

0.0761

Gnomad4 AMR

AF:

0.250

Gnomad4 ASJ

AF:

0.351

Gnomad4 EAS

AF:

0.194

Gnomad4 SAS

AF:

0.317

Gnomad4 FIN

AF:

0.318

Gnomad4 NFE

AF:

0.331

Gnomad4 OTH

AF:

0.282

Alfa

AF:

0.315

Hom.:

16621

Bravo

AF:

0.230

TwinsUK

AF:

0.316

AC:

1172

ALSPAC

AF:

0.326

AC:

1257

ESP6500AA

AF:

0.0840

AC:

370

ESP6500EA

AF:

0.334

AC:

2876

ExAC

AF:

0.286

AC:

34759

Asia WGS

AF:

0.220

AC:

762

AN:

3478

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	clinical testing	GeneDx	May 04, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	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: MAF -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.70

CADD

Uncertain

DANN

Benign

0.29

DEOGEN2

Benign

0.062

T;.;.

Eigen

Benign

0.17

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.95

D;T;D

MetaRNN

Benign

0.0017

T;T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

1.6

L;.;.

MutationTaster

Benign

9.4e-25

P;P;P

PrimateAI

Uncertain

0.66

PROVEAN

Uncertain

-4.0

D;N;.

REVEL

Benign

0.13

Sift

Benign

0.088

T;T;.

Sift4G

Benign

0.12

.;.;T

Polyphen

0.19

B;.;.

Vest4

0.26

MPC

0.13

ClinPred

0.041

GERP RS

3.8

Varity_R

0.37

gMVP

0.28

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.28

dbscSNV1_RF

Benign

0.49

SpliceAI score (max)

0.010

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