7-21899414-C-A

Variant names:

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001277115.2(DNAH11):c.13128C>A(p.Leu4376Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.297 in 1,613,276 control chromosomes in the GnomAD database, including 74,262 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.25 ( 5447 hom., cov: 32)

Exomes 𝑓: 0.30 ( 68815 hom. )

Consequence

DNAH11
NM_001277115.2 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -1.49

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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.39).

BP6

Variant 7-21899414-C-A is Benign according to our data. Variant chr7-21899414-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 178739.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-21899414-C-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-1.49 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.312 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH11	NM_001277115.2 link	c.13128C>A	p.Leu4376Leu	synonymous_variant	Exon 80 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.13128C>A	p.Leu4376Leu	synonymous_variant	Exon 80 of 82	5	NM_001277115.2	ENSP00000475939.1		Q96DT5
DNAH11	ENST00000479878.1 link	n.499C>A		non_coding_transcript_exon_variant	Exon 3 of 5	3

Frequencies

GnomAD3 genomes

AF:

0.247

AC:

37512

AN:

151982

Hom.:

5451

Cov.:

show subpopulations

Gnomad AFR

AF:

0.102

Gnomad AMI

AF:

0.202

Gnomad AMR

AF:

0.275

Gnomad ASJ

AF:

0.393

Gnomad EAS

AF:

0.161

Gnomad SAS

AF:

0.227

Gnomad FIN

AF:

0.331

Gnomad MID

AF:

0.266

Gnomad NFE

AF:

0.316

Gnomad OTH

AF:

0.266

GnomAD3 exomes

AF:

0.277

AC:

68923

AN:

248912

Hom.:

10214

AF XY:

0.282

AC XY:

38045

AN XY:

135066

show subpopulations

Gnomad AFR exome

AF:

0.0950

Gnomad AMR exome

AF:

0.253

Gnomad ASJ exome

AF:

0.391

Gnomad EAS exome

AF:

0.168

Gnomad SAS exome

AF:

0.244

Gnomad FIN exome

AF:

0.318

Gnomad NFE exome

AF:

0.316

Gnomad OTH exome

AF:

0.294

GnomAD4 exome

AF:

0.302

AC:

441599

AN:

1461174

Hom.:

68815

Cov.:

AF XY:

0.301

AC XY:

218598

AN XY:

726912

show subpopulations

Gnomad4 AFR exome

AF:

0.0929

Gnomad4 AMR exome

AF:

0.259

Gnomad4 ASJ exome

AF:

0.387

Gnomad4 EAS exome

AF:

0.166

Gnomad4 SAS exome

AF:

0.244

Gnomad4 FIN exome

AF:

0.322

Gnomad4 NFE exome

AF:

0.317

Gnomad4 OTH exome

AF:

0.293

GnomAD4 genome

AF:

0.247

AC:

37499

AN:

152102

Hom.:

5447

Cov.:

AF XY:

0.247

AC XY:

18339

AN XY:

74316

show subpopulations

Gnomad4 AFR

AF:

0.102

Gnomad4 AMR

AF:

0.274

Gnomad4 ASJ

AF:

0.393

Gnomad4 EAS

AF:

0.161

Gnomad4 SAS

AF:

0.227

Gnomad4 FIN

AF:

0.331

Gnomad4 NFE

AF:

0.316

Gnomad4 OTH

AF:

0.264

Alfa

AF:

0.292

Hom.:

10523

Bravo

AF:

0.236

Asia WGS

AF:

0.184

AC:

641

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: no assertion criteria provided

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

Leu4376Leu in exon 80 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 32.3% (2682/8308) of European American chromosomes from a broad population by the NHLBI Exome Seq uencing Project (http://evs.gs.washington.edu/EVS; dbSNP rs56333627). -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

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

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

- -

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

BayesDel_noAF

Benign

-0.39

CADD

Benign

0.21

DANN

Benign

0.87

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