rs62441683

Positions:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001277115.2(DNAH11):c.1961C>G(p.Ser654Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 1,609,436 control chromosomes in the GnomAD database, including 19,431 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 Likely benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 1279 hom., cov: 32)

Exomes 𝑓: 0.15 ( 18152 hom. )

Consequence

DNAH11
NM_001277115.2 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 1.78

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=0.0017820597).

BP6

Variant 7-21588624-C-G is Benign according to our data. Variant chr7-21588624-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 163098.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-21588624-C-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.164 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH11	NM_001277115.2 linkuse as main transcript	c.1961C>G	p.Ser654Cys	missense_variant	11/82	ENST00000409508.8	NP_001264044.1	Q96DT5Q96NT7H9NAJ8H9NAJ7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAH11	ENST00000409508.8 linkuse as main transcript	c.1961C>G	p.Ser654Cys	missense_variant	11/82	5	NM_001277115.2	ENSP00000475939.1		Q96DT5

Frequencies

GnomAD3 genomes

AF:

0.114

AC:

17357

AN:

152108

Hom.:

1279

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0292

Gnomad AMI

AF:

0.0395

Gnomad AMR

AF:

0.114

Gnomad ASJ

AF:

0.187

Gnomad EAS

AF:

0.0343

Gnomad SAS

AF:

0.107

Gnomad FIN

AF:

0.126

Gnomad MID

AF:

0.174

Gnomad NFE

AF:

0.167

Gnomad OTH

AF:

0.140

GnomAD3 exomes

AF:

0.124

AC:

30803

AN:

248726

Hom.:

2298

AF XY:

0.129

AC XY:

17447

AN XY:

134928

show subpopulations

Gnomad AFR exome

AF:

0.0247

Gnomad AMR exome

AF:

0.0751

Gnomad ASJ exome

AF:

0.178

Gnomad EAS exome

AF:

0.0309

Gnomad SAS exome

AF:

0.114

Gnomad FIN exome

AF:

0.119

Gnomad NFE exome

AF:

0.165

Gnomad OTH exome

AF:

0.140

GnomAD4 exome

AF:

0.152

AC:

220923

AN:

1457210

Hom.:

18152

Cov.:

AF XY:

0.151

AC XY:

109822

AN XY:

725084

show subpopulations

Gnomad4 AFR exome

AF:

0.0234

Gnomad4 AMR exome

AF:

0.0803

Gnomad4 ASJ exome

AF:

0.181

Gnomad4 EAS exome

AF:

0.0241

Gnomad4 SAS exome

AF:

0.115

Gnomad4 FIN exome

AF:

0.121

Gnomad4 NFE exome

AF:

0.167

Gnomad4 OTH exome

AF:

0.143

GnomAD4 genome

AF:

0.114

AC:

17355

AN:

152226

Hom.:

1279

Cov.:

AF XY:

0.111

AC XY:

8294

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.0292

Gnomad4 AMR

AF:

0.114

Gnomad4 ASJ

AF:

0.187

Gnomad4 EAS

AF:

0.0344

Gnomad4 SAS

AF:

0.107

Gnomad4 FIN

AF:

0.126

Gnomad4 NFE

AF:

0.167

Gnomad4 OTH

AF:

0.137

Alfa

AF:

0.154

Hom.:

1513

Bravo

AF:

0.110

TwinsUK

AF:

0.182

AC:

675

ALSPAC

AF:

0.164

AC:

633

ESP6500AA

AF:

0.0270

AC:

101

ESP6500EA

AF:

0.168

AC:

1378

ExAC

AF:

0.125

AC:

15090

Asia WGS

AF:

0.0520

AC:

183

AN:

3478

EpiCase

AF:

0.174

EpiControl

AF:

0.175

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Feb 21, 2013	Ser654Cys in exon 11 of DNAH11: This variant is not expected to have clinical si gnificance because it has been identified in 16.8% (1378/8220) of European Ameri can chromosomes from a broad population by the NHLBI Exome Sequencing Project (h ttp://evs.gs.washington.edu/EVS; dbSNP rs62441683). -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Primary ciliary dyskinesia

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 07, 2019	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Primary ciliary dyskinesia 7

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.098

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Benign

0.66

DEOGEN2

Benign

0.14

.;.;T

Eigen

Benign

0.089

Eigen_PC

Benign

0.061

FATHMM_MKL

Benign

0.72

LIST_S2

Benign

0.69

T;T;T

MetaRNN

Benign

0.0018

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

.;.;L

PrimateAI

Benign

0.32

PROVEAN

Uncertain

-2.4

.;N;.

REVEL

Benign

0.26

Sift

Benign

0.14

.;T;.

Polyphen

0.96

.;.;D

Vest4

0.15

ClinPred

0.022

GERP RS

3.7

Varity_R

0.16

gMVP

0.12

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