rs6965750

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001277115.2(DNAH11):c.9561G>A(p.Leu3187Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 1,612,302 control chromosomes in the GnomAD database, including 16,565 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. L3187L) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.15 ( 1763 hom., cov: 33)

Exomes 𝑓: 0.14 ( 14802 hom. )

Consequence

DNAH11
NM_001277115.2 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.298

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 was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.35).

BP6

Variant 7-21784504-G-A is Benign according to our data. Variant chr7-21784504-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 178731.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-21784504-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.298 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.189 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH11	NM_001277115.2 link	c.9561G>A	p.Leu3187Leu	synonymous_variant	Exon 58 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.9561G>A	p.Leu3187Leu	synonymous_variant	Exon 58 of 82	5	NM_001277115.2	ENSP00000475939.1		Q96DT5

Frequencies

GnomAD3 genomes

AF:

0.147

AC:

22342

AN:

152066

Hom.:

1759

Cov.:

show subpopulations

Gnomad AFR

AF:

0.193

Gnomad AMI

AF:

0.0727

Gnomad AMR

AF:

0.0890

Gnomad ASJ

AF:

0.148

Gnomad EAS

AF:

0.0619

Gnomad SAS

AF:

0.118

Gnomad FIN

AF:

0.138

Gnomad MID

AF:

0.146

Gnomad NFE

AF:

0.143

Gnomad OTH

AF:

0.125

GnomAD2 exomes

AF:

0.124

AC:

30769

AN:

247318

AF XY:

0.126

show subpopulations

Gnomad AFR exome

AF:

0.197

Gnomad AMR exome

AF:

0.0533

Gnomad ASJ exome

AF:

0.141

Gnomad EAS exome

AF:

0.0680

Gnomad FIN exome

AF:

0.143

Gnomad NFE exome

AF:

0.141

Gnomad OTH exome

AF:

0.124

GnomAD4 exome

AF:

0.139

AC:

203401

AN:

1460118

Hom.:

14802

Cov.:

AF XY:

0.139

AC XY:

100991

AN XY:

726254

show subpopulations

Gnomad4 AFR exome

AF:

0.192

AC:

6423

AN:

33438

Gnomad4 AMR exome

AF:

0.0580

AC:

2588

AN:

44590

Gnomad4 ASJ exome

AF:

0.144

AC:

3762

AN:

26108

Gnomad4 EAS exome

AF:

0.0532

AC:

2110

AN:

39646

Gnomad4 SAS exome

AF:

0.123

AC:

10571

AN:

85970

Gnomad4 FIN exome

AF:

0.144

AC:

7675

AN:

53338

Gnomad4 NFE exome

AF:

0.145

AC:

161378

AN:

1110940

Gnomad4 Remaining exome

AF:

0.137

AC:

8257

AN:

60324

Heterozygous variant carriers

7879

15757

23636

31514

39393

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

5812

11624

17436

23248

29060

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.147

AC:

22353

AN:

152184

Hom.:

1763

Cov.:

AF XY:

0.143

AC XY:

10657

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.193

AC:

0.192775

AN:

0.192775

Gnomad4 AMR

AF:

0.0888

AC:

0.0887973

AN:

0.0887973

Gnomad4 ASJ

AF:

0.148

AC:

0.14755

AN:

0.14755

Gnomad4 EAS

AF:

0.0621

AC:

0.0620902

AN:

0.0620902

Gnomad4 SAS

AF:

0.119

AC:

0.119087

AN:

0.119087

Gnomad4 FIN

AF:

0.138

AC:

0.138302

AN:

0.138302

Gnomad4 NFE

AF:

0.143

AC:

0.143368

AN:

0.143368

Gnomad4 OTH

AF:

0.124

AC:

0.123819

AN:

0.123819

Heterozygous variant carriers

967

1934

2900

3867

4834

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

248

496

744

992

1240

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.138

Hom.:

6587

Bravo

AF:

0.145

Asia WGS

AF:

0.0970

AC:

340

AN:

3476

EpiCase

AF:

0.140

EpiControl

AF:

0.142

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 21, 2013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Leu3187Leu in exon 58 of DNAH11: This variant is not expected to have clinical s ignificance because it does not alter an amino acid residue and is not located w ithin the splice consensus sequence. It has been identified in 17.7% (695/3924) of African American chromosomes from a broad population by the NHLBI Exome Seque ncing Project (http://evs.gs.washington.edu/EVS; dbSNP rs6965750). -

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

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Nov 10, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.35

CADD

Benign

5.6

DANN

Benign

0.86

Mutation Taster

=100/0

polymorphism (auto)

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