rs117064287

Variant names:

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_001277115.2(DNAH11):c.640A>G(p.Ile214Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00629 in 1,595,426 control chromosomes in the GnomAD database, including 59 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0056 ( 5 hom., cov: 33)

Exomes 𝑓: 0.0064 ( 54 hom. )

Consequence

DNAH11
NM_001277115.2 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:6

Conservation

PhyloP100: 2.94

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 -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006872803).

BP6

Variant 7-21558946-A-G is Benign according to our data. Variant chr7-21558946-A-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 166998.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=3, Benign=3, Uncertain_significance=1}.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00563 (857/152324) while in subpopulation NFE AF= 0.0092 (626/68014). AF 95% confidence interval is 0.00861. There are 5 homozygotes in gnomad4. There are 430 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH11	NM_001277115.2 link	c.640A>G	p.Ile214Val	missense_variant	Exon 3 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.640A>G	p.Ile214Val	missense_variant	Exon 3 of 82	5	NM_001277115.2	ENSP00000475939.1		Q96DT5

Frequencies

GnomAD3 genomes

AF:

0.00562

AC:

856

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00133

Gnomad AMI

AF:

0.0154

Gnomad AMR

AF:

0.00111

Gnomad ASJ

AF:

0.00374

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0114

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00920

Gnomad OTH

AF:

0.00430

GnomAD3 exomes

AF:

0.00546

AC:

1199

AN:

219534

Hom.:

AF XY:

0.00532

AC XY:

627

AN XY:

117788

show subpopulations

Gnomad AFR exome

AF:

0.00113

Gnomad AMR exome

AF:

0.000832

Gnomad ASJ exome

AF:

0.00436

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000598

Gnomad FIN exome

AF:

0.0129

Gnomad NFE exome

AF:

0.00832

Gnomad OTH exome

AF:

0.00619

GnomAD4 exome

AF:

0.00636

AC:

9180

AN:

1443102

Hom.:

Cov.:

AF XY:

0.00633

AC XY:

4531

AN XY:

715680

show subpopulations

Gnomad4 AFR exome

AF:

0.000753

Gnomad4 AMR exome

AF:

0.00100

Gnomad4 ASJ exome

AF:

0.00405

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000398

Gnomad4 FIN exome

AF:

0.0137

Gnomad4 NFE exome

AF:

0.00723

Gnomad4 OTH exome

AF:

0.00474

GnomAD4 genome

AF:

0.00563

AC:

857

AN:

152324

Hom.:

Cov.:

AF XY:

0.00577

AC XY:

430

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.00132

Gnomad4 AMR

AF:

0.00111

Gnomad4 ASJ

AF:

0.00374

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.0114

Gnomad4 NFE

AF:

0.00920

Gnomad4 OTH

AF:

0.00425

Alfa

AF:

0.00756

Hom.:

Bravo

AF:

0.00411

TwinsUK

AF:

0.00647

AC:

ALSPAC

AF:

0.00675

AC:

ESP6500AA

AF:

0.00241

AC:

ESP6500EA

AF:

0.00732

AC:

ExAC

AF:

0.00497

AC:

599

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:6

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Primary ciliary dyskinesia

Uncertain:1Benign:1

Jan 30, 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: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:2

Apr 03, 2014

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Apr 26, 2016

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Jan 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

DNAH11: BP4, BS2 -

Feb 13, 2022

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Primary ciliary dyskinesia 7

Benign:1

Dec 19, 2019

Genetics and Molecular Pathology, SA Pathology

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.038

.;.;T

Eigen

Benign

-0.067

Eigen_PC

Benign

0.14

FATHMM_MKL

Benign

0.75

LIST_S2

Benign

0.52

T;T;T

MetaRNN

Benign

0.0069

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.4

.;.;M

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.80

.;N;.

REVEL

Benign

0.042

Sift

Benign

0.054

.;T;.

Polyphen

0.0010

.;.;B

Vest4

0.27

MVP

0.16

ClinPred

0.029

GERP RS

6.0

Varity_R

0.033

gMVP

0.10

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