rs2003417

Variant names:

Variant summary

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

The NM_001277115.2(DNAH11):c.7756T>C(p.Tyr2586His) variant causes a missense change. The variant allele was found at a frequency of 0.0508 in 1,604,626 control chromosomes in the GnomAD database, including 2,372 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.034 ( 132 hom., cov: 32)

Exomes 𝑓: 0.053 ( 2240 hom. )

Consequence

DNAH11
NM_001277115.2 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 6.28

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=0.0071105957).

BP6

Variant 7-21738811-T-C is Benign according to our data. Variant chr7-21738811-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 163111.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-21738811-T-C is described in Lovd as [Benign]. Variant chr7-21738811-T-C is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0544 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH11	NM_001277115.2 link	c.7756T>C	p.Tyr2586His	missense_variant	Exon 47 of 82	ENST00000409508.8	NP_001264044.1	Q96DT5Q96NT7H9NAJ8H9NAJ7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH11	ENST00000409508.8 link	c.7756T>C	p.Tyr2586His	missense_variant	Exon 47 of 82	5	NM_001277115.2	ENSP00000475939.1		Q96DT5
DNAH11	ENST00000605912.1 link	c.316T>C	p.Tyr106His	missense_variant	Exon 2 of 4	3		ENSP00000476068.1		U3KQN2

Frequencies

GnomAD3 genomes

AF:

0.0344

AC:

5235

AN:

152130

Hom.:

132

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00987

Gnomad AMI

AF:

0.0186

Gnomad AMR

AF:

0.0200

Gnomad ASJ

AF:

0.0225

Gnomad EAS

AF:

0.00116

Gnomad SAS

AF:

0.0230

Gnomad FIN

AF:

0.0418

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0559

Gnomad OTH

AF:

0.0287

GnomAD3 exomes

AF:

0.0374

AC:

8811

AN:

235612

Hom.:

234

AF XY:

0.0377

AC XY:

4789

AN XY:

127106

show subpopulations

Gnomad AFR exome

AF:

0.00878

Gnomad AMR exome

AF:

0.0223

Gnomad ASJ exome

AF:

0.0219

Gnomad EAS exome

AF:

0.0000572

Gnomad SAS exome

AF:

0.0264

Gnomad FIN exome

AF:

0.0416

Gnomad NFE exome

AF:

0.0559

Gnomad OTH exome

AF:

0.0341

GnomAD4 exome

AF:

0.0526

AC:

76332

AN:

1452378

Hom.:

2240

Cov.:

AF XY:

0.0516

AC XY:

37214

AN XY:

721364

show subpopulations

Gnomad4 AFR exome

AF:

0.00762

Gnomad4 AMR exome

AF:

0.0216

Gnomad4 ASJ exome

AF:

0.0248

Gnomad4 EAS exome

AF:

0.0000759

Gnomad4 SAS exome

AF:

0.0283

Gnomad4 FIN exome

AF:

0.0420

Gnomad4 NFE exome

AF:

0.0606

Gnomad4 OTH exome

AF:

0.0462

GnomAD4 genome

AF:

0.0344

AC:

5231

AN:

152248

Hom.:

132

Cov.:

AF XY:

0.0327

AC XY:

2433

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.00984

Gnomad4 AMR

AF:

0.0199

Gnomad4 ASJ

AF:

0.0225

Gnomad4 EAS

AF:

0.00116

Gnomad4 SAS

AF:

0.0226

Gnomad4 FIN

AF:

0.0418

Gnomad4 NFE

AF:

0.0559

Gnomad4 OTH

AF:

0.0284

Alfa

AF:

0.0500

Hom.:

348

Bravo

AF:

0.0324

TwinsUK

AF:

0.0623

AC:

231

ALSPAC

AF:

0.0649

AC:

250

ESP6500AA

AF:

0.0152

AC:

ESP6500EA

AF:

0.0550

AC:

471

ExAC

AF:

0.0375

AC:

4542

Asia WGS

AF:

0.00751

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Feb 21, 2013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Tyr2586His in exon 47 of DNAH11: This variant is not expected to have clinical s ignificance because it has been identified in 5.5% (471/8562) of European Americ an chromosomes from a broad population by the NHLBI Exome Sequencing Project (ht tp://evs.gs.washington.edu/EVS; dbSNP rs2003417). -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Primary ciliary dyskinesia

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 05, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.38

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.20

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.54

.;.;D;.

Eigen

Uncertain

0.52

Eigen_PC

Uncertain

0.46

FATHMM_MKL

Uncertain

0.96

LIST_S2

Pathogenic

0.99

D;D;D;D

MetaRNN

Benign

0.0071

T;T;T;T

MetaSVM

Benign

-0.77

PrimateAI

Uncertain

0.52

PROVEAN

Pathogenic

-4.7

.;D;.;.

REVEL

Uncertain

0.43

Sift

Pathogenic

0.0

.;D;.;.

Sift4G

Pathogenic

0.0

.;.;.;D

Vest4

0.21

ClinPred

0.053

GERP RS

5.4

Varity_R

0.76

gMVP

0.59

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