7-21742035-A-G

Variant names:

Variant summary

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

The NM_001277115.2(DNAH11):c.8023A>G(p.Ile2675Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00161 in 1,613,914 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I2675F) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0032 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0015 ( 8 hom. )

Consequence

DNAH11
NM_001277115.2 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:4

Conservation

PhyloP100: 0.670

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=0.0054730177).

BP6

Variant 7-21742035-A-G is Benign according to our data. Variant chr7-21742035-A-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 257933.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=3, Benign=1, Uncertain_significance=2}.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00315 (480/152266) while in subpopulation AFR AF= 0.00815 (339/41572). AF 95% confidence interval is 0.00744. There are 1 homozygotes in gnomad4. There are 240 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH11	NM_001277115.2 link	c.8023A>G	p.Ile2675Val	missense_variant	Exon 49 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.8023A>G	p.Ile2675Val	missense_variant	Exon 49 of 82	5	NM_001277115.2	ENSP00000475939.1		Q96DT5
DNAH11	ENST00000605912.1 link	c.474+2362A>G		intron_variant	Intron 3 of 3	3		ENSP00000476068.1		U3KQN2

Frequencies

GnomAD3 genomes

AF:

0.00314

AC:

477

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00811

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00282

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00462

Gnomad SAS

AF:

0.000830

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000853

Gnomad OTH

AF:

0.00430

GnomAD3 exomes

AF:

0.00176

AC:

438

AN:

249166

Hom.:

AF XY:

0.00164

AC XY:

222

AN XY:

135160

show subpopulations

Gnomad AFR exome

AF:

0.00756

Gnomad AMR exome

AF:

0.00345

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00228

Gnomad SAS exome

AF:

0.000523

Gnomad FIN exome

AF:

0.0000464

Gnomad NFE exome

AF:

0.00112

Gnomad OTH exome

AF:

0.00298

GnomAD4 exome

AF:

0.00145

AC:

2120

AN:

1461648

Hom.:

Cov.:

AF XY:

0.00144

AC XY:

1044

AN XY:

727112

show subpopulations

Gnomad4 AFR exome

AF:

0.00759

Gnomad4 AMR exome

AF:

0.00371

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0102

Gnomad4 SAS exome

AF:

0.000522

Gnomad4 FIN exome

AF:

0.0000749

Gnomad4 NFE exome

AF:

0.000991

Gnomad4 OTH exome

AF:

0.00200

GnomAD4 genome

AF:

0.00315

AC:

480

AN:

152266

Hom.:

Cov.:

AF XY:

0.00322

AC XY:

240

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.00815

Gnomad4 AMR

AF:

0.00281

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00463

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.000853

Gnomad4 OTH

AF:

0.00426

Alfa

AF:

0.00114

Hom.:

Bravo

AF:

0.00375

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.00737

AC:

ESP6500EA

AF:

0.000846

AC:

ExAC

AF:

0.00204

AC:

246

EpiCase

AF:

0.00120

EpiControl

AF:

0.00119

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:2Benign:4

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Primary ciliary dyskinesia 7

Uncertain:1Benign:1

May 11, 2018

Baylor Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. -

Mar 08, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Primary ciliary dyskinesia

Uncertain:1Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely 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:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Dec 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

DNAH11: BP4 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.71

CADD

Benign

0.16

DANN

Benign

0.17

DEOGEN2

Benign

0.036

.;.;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.34

T;T;T

M_CAP

Benign

0.0011

MetaRNN

Benign

0.0055

T;T;T

MetaSVM

Benign

-0.99

PrimateAI

Benign

0.24

PROVEAN

Benign

0.26

.;N;.

REVEL

Benign

0.014

Sift

Benign

1.0

.;T;.

Vest4

0.10

MVP

0.12

ClinPred

0.000013

GERP RS

-1.3

Varity_R

0.021

gMVP

0.22

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