rs28751578

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.9098T>C(p.Ile3033Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00311 in 1,576,640 control chromosomes in the GnomAD database, including 151 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 Likely benign (★★).

Frequency

Genomes: 𝑓 0.016 ( 71 hom., cov: 31)

Exomes 𝑓: 0.0017 ( 80 hom. )

Consequence

DNAH11
NM_001277115.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 4.84

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=0.003173232).

BP6

Variant 7-21765585-T-C is Benign according to our data. Variant chr7-21765585-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 238940.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0549 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH11	NM_001277115.2 link	c.9098T>C	p.Ile3033Thr	missense_variant	Exon 55 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.9098T>C	p.Ile3033Thr	missense_variant	Exon 55 of 82	5	NM_001277115.2	ENSP00000475939.1		Q96DT5

Frequencies

GnomAD3 genomes

AF:

0.0162

AC:

2389

AN:

147518

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0567

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00461

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000659

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00325

Gnomad NFE

AF:

0.000149

Gnomad OTH

AF:

0.0134

GnomAD3 exomes

AF:

0.00388

AC:

928

AN:

239040

Hom.:

AF XY:

0.00318

AC XY:

413

AN XY:

129836

show subpopulations

Gnomad AFR exome

AF:

0.0551

Gnomad AMR exome

AF:

0.00219

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000574

Gnomad SAS exome

AF:

0.000235

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000837

Gnomad OTH exome

AF:

0.00170

GnomAD4 exome

AF:

0.00175

AC:

2500

AN:

1428996

Hom.:

Cov.:

AF XY:

0.00149

AC XY:

1059

AN XY:

710008

show subpopulations

Gnomad4 AFR exome

AF:

0.0643

Gnomad4 AMR exome

AF:

0.00238

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000176

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000202

Gnomad4 OTH exome

AF:

0.00398

GnomAD4 genome

AF:

0.0163

AC:

2400

AN:

147644

Hom.:

Cov.:

AF XY:

0.0161

AC XY:

1154

AN XY:

71676

show subpopulations

Gnomad4 AFR

AF:

0.0568

Gnomad4 AMR

AF:

0.00461

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000659

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000149

Gnomad4 OTH

AF:

0.0132

Alfa

AF:

0.00830

Hom.:

Bravo

AF:

0.0182

ESP6500AA

AF:

0.0521

AC:

217

ESP6500EA

AF:

0.000119

AC:

ExAC

AF:

0.00512

AC:

619

Asia WGS

AF:

0.00404

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Primary ciliary dyskinesia

Benign:3

Feb 02, 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

- -

Aug 17, 2015

Ambry Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 28, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.29

.;.;T

Eigen

Benign

-0.19

Eigen_PC

Benign

-0.026

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.69

T;T;T

MetaRNN

Benign

0.0032

T;T;T

MetaSVM

Benign

-1.1

PrimateAI

Benign

0.38

PROVEAN

Uncertain

-3.8

.;D;.

REVEL

Benign

0.087

Sift

Uncertain

0.021

.;D;.

Vest4

0.34

MVP

0.42

ClinPred

0.027

GERP RS

4.5

Varity_R

0.17

gMVP

0.21

Splicing

Name

Calibrated prediction

Score

Prediction

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