rs9639393

Positions:

Variant summary

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

The NM_001277115.2(DNAH11):c.7901A>G(p.Asn2634Ser) variant causes a missense change. The variant allele was found at a frequency of 0.598 in 1,610,198 control chromosomes in the GnomAD database, including 300,973 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.50 ( 21691 hom., cov: 31)

Exomes 𝑓: 0.61 ( 279282 hom. )

Consequence

DNAH11
NM_001277115.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 4.52

Variant links:

Genes affected

DNAH11 (HGNC:2942): (dynein axonemal heavy chain 11) This gene encodes a ciliary outer dynein arm protein and is a member of the dynein heavy chain family. It is a microtubule-dependent motor ATPase and has been reported to be involved in the movement of respiratory cilia. Mutations in this gene have been implicated in causing Kartagener Syndrome (a combination of situs inversus totalis and Primary Ciliary Dyskinesia (PCD), also called Immotile Cilia Syndrome 1 (ICS1)) and male sterility. [provided by RefSeq, Mar 2013]

DNAH11 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=6.6290036E-6).

BP6

Variant 7-21739660-A-G is Benign according to our data. Variant chr7-21739660-A-G is described in ClinVar as [Benign]. Clinvar id is 163113.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-21739660-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.637 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH11	NM_001277115.2 link	c.7901A>G	p.Asn2634Ser	missense_variant	48/82	ENST00000409508.8	NP_001264044.1	Q96DT5Q96NT7H9NAJ8H9NAJ7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAH11	ENST00000409508.8 link	c.7901A>G	p.Asn2634Ser	missense_variant	48/82	5	NM_001277115.2	ENSP00000475939.1		Q96DT5
DNAH11	ENST00000605912.1 link	c.461A>G	p.Asn154Ser	missense_variant	3/4	3		ENSP00000476068.1		U3KQN2

Frequencies

GnomAD3 genomes

AF:

0.503

AC:

76446

AN:

151882

Hom.:

21691

Cov.:

show subpopulations

Gnomad AFR

AF:

0.275

Gnomad AMI

AF:

0.708

Gnomad AMR

AF:

0.516

Gnomad ASJ

AF:

0.544

Gnomad EAS

AF:

0.0805

Gnomad SAS

AF:

0.523

Gnomad FIN

AF:

0.650

Gnomad MID

AF:

0.440

Gnomad NFE

AF:

0.642

Gnomad OTH

AF:

0.523

GnomAD3 exomes

AF:

0.533

AC:

132060

AN:

247692

Hom.:

38870

AF XY:

0.547

AC XY:

73530

AN XY:

134418

show subpopulations

Gnomad AFR exome

AF:

0.261

Gnomad AMR exome

AF:

0.465

Gnomad ASJ exome

AF:

0.531

Gnomad EAS exome

AF:

0.0627

Gnomad SAS exome

AF:

0.551

Gnomad FIN exome

AF:

0.641

Gnomad NFE exome

AF:

0.639

Gnomad OTH exome

AF:

0.565

GnomAD4 exome

AF:

0.608

AC:

886408

AN:

1458198

Hom.:

279282

Cov.:

AF XY:

0.608

AC XY:

441264

AN XY:

725280

show subpopulations

Gnomad4 AFR exome

AF:

0.267

Gnomad4 AMR exome

AF:

0.472

Gnomad4 ASJ exome

AF:

0.528

Gnomad4 EAS exome

AF:

0.111

Gnomad4 SAS exome

AF:

0.558

Gnomad4 FIN exome

AF:

0.641

Gnomad4 NFE exome

AF:

0.648

Gnomad4 OTH exome

AF:

0.562

GnomAD4 genome

AF:

0.503

AC:

76463

AN:

152000

Hom.:

21691

Cov.:

AF XY:

0.501

AC XY:

37218

AN XY:

74304

show subpopulations

Gnomad4 AFR

AF:

0.275

Gnomad4 AMR

AF:

0.515

Gnomad4 ASJ

AF:

0.544

Gnomad4 EAS

AF:

0.0803

Gnomad4 SAS

AF:

0.523

Gnomad4 FIN

AF:

0.650

Gnomad4 NFE

AF:

0.642

Gnomad4 OTH

AF:

0.524

Alfa

AF:

0.601

Hom.:

54351

Bravo

AF:

0.477

TwinsUK

AF:

0.647

AC:

2398

ALSPAC

AF:

0.649

AC:

2503

ESP6500AA

AF:

0.310

AC:

1187

ESP6500EA

AF:

0.634

AC:

5231

ExAC

AF:

0.534

AC:

64469

Asia WGS

AF:

0.320

AC:

1112

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Feb 21, 2013	Asn2634Ser in exon 48 of DNAH11: This variant is not expected to have clinical s ignificance because it has been identified in 36.6% (3021/8252) of European Amer ican chromosomes from a broad population by the NHLBI Exome Sequencing Project ( http://evs.gs.washington.edu/EVS; dbSNP rs9639393). -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Primary ciliary dyskinesia

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 03, 2025	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -

Primary ciliary dyskinesia 7

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.68

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.27

.;.;T;.

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.34

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.68

T;T;T;T

MetaRNN

Benign

0.0000066

T;T;T;T

MetaSVM

Benign

-0.97

PrimateAI

Benign

0.30

PROVEAN

Uncertain

-3.5

.;D;.;.

REVEL

Benign

0.19

Sift

Benign

0.051

.;T;.;.

Sift4G

Benign

0.26

.;.;.;T

Vest4

0.080

ClinPred

0.029

GERP RS

3.3

Varity_R

0.075

gMVP

0.16

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