7-21588619-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001277115.2(DNAH11):c.1956C>T(p.Phe652Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.989 in 1,613,386 control chromosomes in the GnomAD database, including 788,992 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.99 ( 74936 hom., cov: 32)

Exomes 𝑓: 0.99 ( 714056 hom. )

Consequence

DNAH11
NM_001277115.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -0.238

Publications

16 publications found

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 Gene-Disease associations (from GenCC):

primary ciliary dyskinesia 7
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), ClinGen
primary ciliary dyskinesia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

DNAH11 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.49).

BP6

Variant 7-21588619-C-T is Benign according to our data. Variant chr7-21588619-C-T is described in ClinVar as Benign. ClinVar VariationId is 163097.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.238 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.989 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH11	NM_001277115.2 link	c.1956C>T	p.Phe652Phe	synonymous_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.1956C>T	p.Phe652Phe	synonymous_variant	Exon 11 of 82	5	NM_001277115.2	ENSP00000475939.1		Q96DT5

Frequencies

GnomAD3 genomes

AF:

0.992

AC:

150956

AN:

152188

Hom.:

74876

Cov.:

show subpopulations

Gnomad AFR

AF:

0.997

Gnomad AMI

AF:

0.996

Gnomad AMR

AF:

0.991

Gnomad ASJ

AF:

0.988

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

0.981

Gnomad FIN

AF:

0.999

Gnomad MID

AF:

0.984

Gnomad NFE

AF:

0.989

Gnomad OTH

AF:

0.986

GnomAD2 exomes

AF:

0.991

AC:

246596

AN:

248948

AF XY:

0.990

show subpopulations

Gnomad AFR exome

AF:

0.997

Gnomad AMR exome

AF:

0.993

Gnomad ASJ exome

AF:

0.986

Gnomad EAS exome

AF:

1.00

Gnomad FIN exome

AF:

0.997

Gnomad NFE exome

AF:

0.989

Gnomad OTH exome

AF:

0.988

GnomAD4 exome

AF:

0.989

AC:

1444439

AN:

1461080

Hom.:

714056

Cov.:

AF XY:

0.988

AC XY:

718304

AN XY:

726862

show subpopulations

African (AFR)

AF:

0.997

AC:

33374

AN:

33462

American (AMR)

AF:

0.993

AC:

44412

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.987

AC:

25790

AN:

26128

East Asian (EAS)

AF:

1.00

AC:

39669

AN:

39672

South Asian (SAS)

AF:

0.983

AC:

84787

AN:

86240

European-Finnish (FIN)

AF:

0.997

AC:

53206

AN:

53374

Middle Eastern (MID)

AF:

0.976

AC:

5630

AN:

5766

European-Non Finnish (NFE)

AF:

0.988

AC:

1097911

AN:

1111366

Other (OTH)

AF:

0.989

AC:

59660

AN:

60354

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.449

Heterozygous variant carriers

820

1640

2461

3281

4101

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21656

43312

64968

86624

108280

<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:

0.992

AC:

151076

AN:

152306

Hom.:

74936

Cov.:

AF XY:

0.992

AC XY:

73899

AN XY:

74472

show subpopulations

African (AFR)

AF:

0.997

AC:

41446

AN:

41570

American (AMR)

AF:

0.991

AC:

15152

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.988

AC:

3429

AN:

3472

East Asian (EAS)

AF:

1.00

AC:

5178

AN:

5178

South Asian (SAS)

AF:

0.982

AC:

4733

AN:

4822

European-Finnish (FIN)

AF:

0.999

AC:

10605

AN:

10618

Middle Eastern (MID)

AF:

0.980

AC:

288

AN:

294

European-Non Finnish (NFE)

AF:

0.989

AC:

67253

AN:

68034

Other (OTH)

AF:

0.986

AC:

2084

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

125

188

250

313

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

914

1828

2742

3656

4570

<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:

0.989

Hom.:

159515

Bravo

AF:

0.992

Asia WGS

AF:

0.992

AC:

3449

AN:

3478

EpiCase

AF:

0.986

EpiControl

AF:

0.985

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

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

Phe652Phe in exon 11 of DNAH11: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue and is not located wi thin the splice consensus sequence. It has been identified in 1.3% (108/8220) of European American chromosomes from a broad population by the NHLBI Exome Sequen cing Project (http://evs.gs.washington.edu/EVS; dbSNP rs6963535). -

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: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

Dec 19, 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

-0.49

CADD

Benign

2.8

(source)

DANN

Benign

0.46

PhyloP100

-0.24

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over