Genetic Variant DNAH11:p.Phe2430Phe (chr7-21725834-C-T) – ACMG Classification: Benign (-19 pts)

Variant summary

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

The NM_001277115.2(DNAH11):c.7290C>T(p.Phe2430Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.494 in 1,609,990 control chromosomes in the GnomAD database, including 201,438 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.42 ( 14627 hom., cov: 32)

Exomes 𝑓: 0.50 ( 186811 hom. )

Consequence

DNAH11
NM_001277115.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 2.22

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=-0.32).

BP6

Variant 7-21725834-C-T is Benign according to our data. Variant chr7-21725834-C-T is described in ClinVar as [Benign]. Clinvar id is 93694.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-21725834-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=2.22 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.508 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH11	NM_001277115.2 link	c.7290C>T	p.Phe2430Phe	synonymous_variant	Exon 45 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.7290C>T	p.Phe2430Phe	synonymous_variant	Exon 45 of 82	5	NM_001277115.2	ENSP00000475939.1		Q96DT5

Frequencies

GnomAD3 genomes

AF:

0.425

AC:

64490

AN:

151802

Hom.:

14635

Cov.:

show subpopulations

Gnomad AFR

AF:

0.278

Gnomad AMI

AF:

0.530

Gnomad AMR

AF:

0.431

Gnomad ASJ

AF:

0.407

Gnomad EAS

AF:

0.214

Gnomad SAS

AF:

0.515

Gnomad FIN

AF:

0.484

Gnomad MID

AF:

0.392

Gnomad NFE

AF:

0.512

Gnomad OTH

AF:

0.429

GnomAD3 exomes

AF:

0.453

AC:

110673

AN:

244124

Hom.:

26355

AF XY:

0.464

AC XY:

61356

AN XY:

132198

show subpopulations

Gnomad AFR exome

AF:

0.268

Gnomad AMR exome

AF:

0.416

Gnomad ASJ exome

AF:

0.404

Gnomad EAS exome

AF:

0.201

Gnomad SAS exome

AF:

0.524

Gnomad FIN exome

AF:

0.483

Gnomad NFE exome

AF:

0.510

Gnomad OTH exome

AF:

0.465

GnomAD4 exome

AF:

0.501

AC:

730108

AN:

1458070

Hom.:

186811

Cov.:

AF XY:

0.502

AC XY:

364277

AN XY:

724940

show subpopulations

Gnomad4 AFR exome

AF:

0.265

Gnomad4 AMR exome

AF:

0.418

Gnomad4 ASJ exome

AF:

0.402

Gnomad4 EAS exome

AF:

0.228

Gnomad4 SAS exome

AF:

0.533

Gnomad4 FIN exome

AF:

0.484

Gnomad4 NFE exome

AF:

0.523

Gnomad4 OTH exome

AF:

0.474

GnomAD4 genome

AF:

0.424

AC:

64482

AN:

151920

Hom.:

14627

Cov.:

AF XY:

0.424

AC XY:

31437

AN XY:

74222

show subpopulations

Gnomad4 AFR

AF:

0.278

Gnomad4 AMR

AF:

0.430

Gnomad4 ASJ

AF:

0.407

Gnomad4 EAS

AF:

0.215

Gnomad4 SAS

AF:

0.516

Gnomad4 FIN

AF:

0.484

Gnomad4 NFE

AF:

0.512

Gnomad4 OTH

AF:

0.425

Alfa

AF:

0.475

Hom.:

28780

Bravo

AF:

0.410

Asia WGS

AF:

0.318

AC:

1103

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Apr 11, 2013

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

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

Phe2430Phe in exon 45 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 49.2% (4012/8162) of European American chromosomes from a broad population by the NHLBI Exome Seq uencing Project (http://evs.gs.washington.edu/EVS; dbSNP rs12536928). -

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

Significance: Benign

Review Status: no assertion criteria provided

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: 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

- -

not provided

Benign:1

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

-0.32

CADD

Benign

6.6

DANN

Benign

0.76

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