rs199629774

Positions:

chr7-21617725-A-G

Variant summary

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

The NM_001277115.2(DNAH11):c.4202A>G(p.Gln1401Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00154 in 1,613,138 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/17 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 0.0010 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0016 ( 17 hom. )

Consequence

DNAH11
NM_001277115.2 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:4

Conservation

PhyloP100: 5.18

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=0.010043949).

BP6

Variant 7-21617725-A-G is Benign according to our data. Variant chr7-21617725-A-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 257890.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Benign=3, Uncertain_significance=1}. Variant chr7-21617725-A-G is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00102 (155/152356) while in subpopulation SAS AF= 0.00828 (40/4828). AF 95% confidence interval is 0.00625. There are 1 homozygotes in gnomad4. There are 89 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 17 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH11	NM_001277115.2 linkuse as main transcript	c.4202A>G	p.Gln1401Arg	missense_variant	23/82	ENST00000409508.8	NP_001264044.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAH11	ENST00000409508.8 linkuse as main transcript	c.4202A>G	p.Gln1401Arg	missense_variant	23/82	5	NM_001277115.2	ENSP00000475939	P1

Frequencies

GnomAD3 genomes

AF:

0.00102

AC:

156

AN:

152238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000589

Gnomad ASJ

AF:

0.00576

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00807

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00115

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.00236

AC:

584

AN:

247820

Hom.:

AF XY:

0.00289

AC XY:

389

AN XY:

134474

show subpopulations

Gnomad AFR exome

AF:

0.000259

Gnomad AMR exome

AF:

0.000322

Gnomad ASJ exome

AF:

0.00512

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0117

Gnomad FIN exome

AF:

0.0000465

Gnomad NFE exome

AF:

0.00131

Gnomad OTH exome

AF:

0.00200

GnomAD4 exome

AF:

0.00159

AC:

2327

AN:

1460782

Hom.:

Cov.:

AF XY:

0.00191

AC XY:

1388

AN XY:

726650

show subpopulations

Gnomad4 AFR exome

AF:

0.000269

Gnomad4 AMR exome

AF:

0.000269

Gnomad4 ASJ exome

AF:

0.00487

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0112

Gnomad4 FIN exome

AF:

0.000112

Gnomad4 NFE exome

AF:

0.000935

Gnomad4 OTH exome

AF:

0.00177

GnomAD4 genome

AF:

0.00102

AC:

155

AN:

152356

Hom.:

Cov.:

AF XY:

0.00119

AC XY:

AN XY:

74510

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.000588

Gnomad4 ASJ

AF:

0.00576

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00829

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00115

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00142

Hom.:

Bravo

AF:

0.000903

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00145

AC:

ExAC

AF:

0.00255

AC:

308

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.00180

EpiControl

AF:

0.00137

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:4

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Primary ciliary dyskinesia

Uncertain:1Benign:2

Uncertain significance, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -
Benign, criteria provided, single submitter	clinical testing	Ambry Genetics	Jan 15, 2018	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. -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2023

DNAH11: BP4, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.098

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.29

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.41

.;.;T

Eigen

Uncertain

0.25

Eigen_PC

Uncertain

0.28

FATHMM_MKL

Benign

0.75

LIST_S2

Benign

0.85

D;D;T

MetaRNN

Benign

0.010

T;T;T

MetaSVM

Benign

-0.89

MutationTaster

Benign

1.0

PrimateAI

Benign

0.38

PROVEAN

Uncertain

-3.4

.;D;.

REVEL

Benign

0.24

Sift

Benign

0.083

.;T;.

Vest4

0.59

MVP

0.51

ClinPred

0.038

GERP RS

4.5

Varity_R

0.41

gMVP

0.21

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