rs12666072

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001277115.2(DNAH11):c.11325G>A(p.Ala3775Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.054 in 1,613,346 control chromosomes in the GnomAD database, including 4,633 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.056 ( 525 hom., cov: 32)

Exomes 𝑓: 0.054 ( 4108 hom. )

Consequence

DNAH11
NM_001277115.2 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -3.30

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BP6

Variant 7-21861975-G-A is Benign according to our data. Variant chr7-21861975-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 163127.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-21861975-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-3.3 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.193 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH11	NM_001277115.2 link	c.11325G>A	p.Ala3775Ala	synonymous_variant	Exon 69 of 82	ENST00000409508.8	NP_001264044.1	Q96DT5Q96NT7H9NAJ8H9NAJ7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DNAH11	ENST00000409508.8 link	c.11325G>A	p.Ala3775Ala	synonymous_variant	Exon 69 of 82	5	NM_001277115.2	ENSP00000475939.1	Q96DT5
DNAH11	ENST00000421290.1 link	n.508G>A		non_coding_transcript_exon_variant	Exon 4 of 4	4
DNAH11	ENST00000607413.5 link	n.*5G>A		downstream_gene_variant		4

Frequencies

GnomAD3 genomes

AF:

0.0559

AC:

8506

AN:

152120

Hom.:

515

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0120

Gnomad AMI

AF:

0.0132

Gnomad AMR

AF:

0.160

Gnomad ASJ

AF:

0.0450

Gnomad EAS

AF:

0.203

Gnomad SAS

AF:

0.0706

Gnomad FIN

AF:

0.0706

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0458

Gnomad OTH

AF:

0.0545

GnomAD3 exomes

AF:

0.0915

AC:

22686

AN:

248056

Hom.:

2089

AF XY:

0.0828

AC XY:

11138

AN XY:

134588

show subpopulations

Gnomad AFR exome

AF:

0.0108

Gnomad AMR exome

AF:

0.272

Gnomad ASJ exome

AF:

0.0431

Gnomad EAS exome

AF:

0.210

Gnomad SAS exome

AF:

0.0651

Gnomad FIN exome

AF:

0.0719

Gnomad NFE exome

AF:

0.0449

Gnomad OTH exome

AF:

0.0753

GnomAD4 exome

AF:

0.0538

AC:

78670

AN:

1461108

Hom.:

4108

Cov.:

AF XY:

0.0535

AC XY:

38913

AN XY:

726802

show subpopulations

Gnomad4 AFR exome

AF:

0.00795

Gnomad4 AMR exome

AF:

0.261

Gnomad4 ASJ exome

AF:

0.0437

Gnomad4 EAS exome

AF:

0.207

Gnomad4 SAS exome

AF:

0.0632

Gnomad4 FIN exome

AF:

0.0720

Gnomad4 NFE exome

AF:

0.0401

Gnomad4 OTH exome

AF:

0.0552

GnomAD4 genome

AF:

0.0560

AC:

8524

AN:

152238

Hom.:

525

Cov.:

AF XY:

0.0605

AC XY:

4501

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.0120

Gnomad4 AMR

AF:

0.162

Gnomad4 ASJ

AF:

0.0450

Gnomad4 EAS

AF:

0.203

Gnomad4 SAS

AF:

0.0710

Gnomad4 FIN

AF:

0.0706

Gnomad4 NFE

AF:

0.0459

Gnomad4 OTH

AF:

0.0530

Alfa

AF:

0.0512

Hom.:

776

Bravo

AF:

0.0644

Asia WGS

AF:

0.144

AC:

501

AN:

3478

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

Feb 21, 2013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Ala3775Ala in exon 69 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 4.3% (363/8394) o f European American chromosomes from a broad population by the NHLBI Exome Seque ncing Project (http://evs.gs.washington.edu/EVS; dbSNP rs12666072). -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Primary ciliary dyskinesia

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely 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 12, 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

-0.62

CADD

Benign

0.056

DANN

Benign

0.63

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