rs1254903583

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001277115.2(DNAH11):c.5068C>A(p.Gln1690Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000412 in 1,455,068 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

DNAH11
NM_001277115.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 0.0430

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

primary ciliary dyskinesia 7
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), ClinGen
primary ciliary dyskinesia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

DNAH11 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.08572608).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH11	NM_001277115.2 link	c.5068C>A	p.Gln1690Lys	missense_variant	Exon 29 of 82	ENST00000409508.8	NP_001264044.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH11	ENST00000409508.8 link	c.5068C>A	p.Gln1690Lys	missense_variant	Exon 29 of 82	5	NM_001277115.2	ENSP00000475939.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000410

AC:

AN:

244082

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000899

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000412

AC:

AN:

1455068

Hom.:

Cov.:

AF XY:

0.00000415

AC XY:

AN XY:

723068

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33270

American (AMR)

AF:

0.00

AC:

AN:

44162

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25920

East Asian (EAS)

AF:

0.00

AC:

AN:

39506

South Asian (SAS)

AF:

0.00

AC:

AN:

84900

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53262

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5730

European-Non Finnish (NFE)

AF:

0.00000541

AC:

AN:

1108184

Other (OTH)

AF:

0.00

AC:

AN:

60134

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.433

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Primary ciliary dyskinesia

Uncertain:2

Dec 08, 2021

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The p.Q1690K variant (also known as c.5068C>A), located in coding exon 29 of the DNAH11 gene, results from a C to A substitution at nucleotide position 5068. The glutamine at codon 1690 is replaced by lysine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. -

Apr 25, 2017

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This sequence change replaces glutamine with lysine at codon 1690 of the DNAH11 protein (p.Gln1690Lys). The glutamine residue is moderately conserved and there is a small physicochemical difference between glutamine and lysine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a DNAH11-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies. In summary, this variant is a novel missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.58

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.070

.;.;T

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.52

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.85

D;D;D

M_CAP

Benign

0.012

MetaRNN

Benign

0.086

T;T;T

MetaSVM

Benign

-0.98

PhyloP100

0.043

PrimateAI

Benign

0.28

PROVEAN

Benign

-1.1

.;N;.

REVEL

Benign

0.076

Sift

Benign

0.45

.;T;.

Vest4

0.35

MutPred

0.51

Gain of sheet (P = 0.0028);Gain of sheet (P = 0.0028);.;

MVP

0.41

ClinPred

0.067

GERP RS

2.9

Varity_R

0.19

gMVP

0.23

Mutation Taster

=90/10

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over