rs12670130

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

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

The NM_001277115.2(DNAH11):c.1916A>G(p.Gln639Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.16 in 1,612,248 control chromosomes in the GnomAD database, including 21,350 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.15 ( 1762 hom., cov: 33)

Exomes 𝑓: 0.16 ( 19588 hom. )

Consequence

DNAH11
NM_001277115.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.88

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=0.0027352571).

BP6

Variant 7-21588579-A-G is Benign according to our data. Variant chr7-21588579-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 163096.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-21588579-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.186 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH11	NM_001277115.2 link	c.1916A>G	p.Gln639Arg	missense_variant	Exon 11 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.1916A>G	p.Gln639Arg	missense_variant	Exon 11 of 82	5	NM_001277115.2	ENSP00000475939.1		Q96DT5

Frequencies

GnomAD3 genomes

AF:

0.151

AC:

23006

AN:

152146

Hom.:

1762

Cov.:

show subpopulations

Gnomad AFR

AF:

0.134

Gnomad AMI

AF:

0.0395

Gnomad AMR

AF:

0.126

Gnomad ASJ

AF:

0.194

Gnomad EAS

AF:

0.196

Gnomad SAS

AF:

0.122

Gnomad FIN

AF:

0.128

Gnomad MID

AF:

0.172

Gnomad NFE

AF:

0.168

Gnomad OTH

AF:

0.174

GnomAD3 exomes

AF:

0.146

AC:

36443

AN:

248812

Hom.:

2909

AF XY:

0.149

AC XY:

20115

AN XY:

134988

show subpopulations

Gnomad AFR exome

AF:

0.131

Gnomad AMR exome

AF:

0.0817

Gnomad ASJ exome

AF:

0.188

Gnomad EAS exome

AF:

0.198

Gnomad SAS exome

AF:

0.126

Gnomad FIN exome

AF:

0.123

Gnomad NFE exome

AF:

0.166

Gnomad OTH exome

AF:

0.151

GnomAD4 exome

AF:

0.161

AC:

235078

AN:

1459984

Hom.:

19588

Cov.:

AF XY:

0.160

AC XY:

116533

AN XY:

726350

show subpopulations

Gnomad4 AFR exome

AF:

0.126

Gnomad4 AMR exome

AF:

0.0880

Gnomad4 ASJ exome

AF:

0.190

Gnomad4 EAS exome

AF:

0.161

Gnomad4 SAS exome

AF:

0.127

Gnomad4 FIN exome

AF:

0.125

Gnomad4 NFE exome

AF:

0.168

Gnomad4 OTH exome

AF:

0.162

GnomAD4 genome

AF:

0.151

AC:

23008

AN:

152264

Hom.:

1762

Cov.:

AF XY:

0.148

AC XY:

11011

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.134

Gnomad4 AMR

AF:

0.125

Gnomad4 ASJ

AF:

0.194

Gnomad4 EAS

AF:

0.196

Gnomad4 SAS

AF:

0.122

Gnomad4 FIN

AF:

0.128

Gnomad4 NFE

AF:

0.168

Gnomad4 OTH

AF:

0.170

Alfa

AF:

0.163

Hom.:

4410

Bravo

AF:

0.152

TwinsUK

AF:

0.182

AC:

675

ALSPAC

AF:

0.165

AC:

634

ESP6500AA

AF:

0.126

AC:

469

ESP6500EA

AF:

0.169

AC:

1393

ExAC

AF:

0.149

AC:

17988

Asia WGS

AF:

0.129

AC:

449

AN:

3478

EpiCase

AF:

0.176

EpiControl

AF:

0.177

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

Feb 21, 2013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Gln639Arg in exon 11 of DNAH11: This variant is not expected to have clinical si gnificance because it has been identified in 16.9% (1393/8222) of European Ameri can chromosomes from a broad population by the NHLBI Exome Sequencing Project (h ttp://evs.gs.washington.edu/EVS; dbSNP rs12670130). -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Primary ciliary dyskinesia

Benign:2

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Jan 21, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Primary ciliary dyskinesia 7

Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Benign

-0.76

BayesDel_noAF

Benign

-0.72

CADD

Benign

8.8

DANN

Benign

0.23

DEOGEN2

Benign

0.042

.;.;T

Eigen

Benign

-0.84

Eigen_PC

Benign

-0.81

FATHMM_MKL

Benign

0.55

LIST_S2

Benign

0.36

T;T;T

MetaRNN

Benign

0.0027

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.15

.;.;N

PrimateAI

Benign

0.21

PROVEAN

Benign

-0.97

.;N;.

REVEL

Benign

0.14

Sift

Benign

0.72

.;T;.

Polyphen

0.0

.;.;B

Vest4

0.012

ClinPred

0.00042

GERP RS

0.13

Varity_R

0.045

gMVP

0.16

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