rs72657374

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_001277115.2(DNAH11):c.9102+8G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0162 in 1,548,870 control chromosomes in the GnomAD database, including 278 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.015 ( 18 hom., cov: 31)

Exomes 𝑓: 0.016 ( 260 hom. )

Consequence

DNAH11
NM_001277115.2 splice_region, intron

Scores

Splicing: ADA: 0.0001321

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:5

Conservation

PhyloP100: -0.150

Publications

2 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 -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.7).

BP6

Variant 7-21765597-G-A is Benign according to our data. Variant chr7-21765597-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 178729.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0146 (2119/144746) while in subpopulation NFE AF = 0.0186 (1232/66088). AF 95% confidence interval is 0.0178. There are 18 homozygotes in GnomAd4. There are 951 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 18 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH11	NM_001277115.2 link	c.9102+8G>A		splice_region_variant, intron_variant	Intron 55 of 81	ENST00000409508.8	NP_001264044.1	Q96DT5Q96NT7H9NAJ8H9NAJ7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH11	ENST00000409508.8 link	c.9102+8G>A		splice_region_variant, intron_variant	Intron 55 of 81	5	NM_001277115.2	ENSP00000475939.1		Q96DT5

Frequencies

GnomAD3 genomes

AF:

0.0147

AC:

2119

AN:

144622

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0125

Gnomad AMI

AF:

0.0113

Gnomad AMR

AF:

0.0162

Gnomad ASJ

AF:

0.00789

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00432

Gnomad FIN

AF:

0.00801

Gnomad MID

AF:

0.0197

Gnomad NFE

AF:

0.0186

Gnomad OTH

AF:

0.0174

GnomAD2 exomes

AF:

0.0121

AC:

2495

AN:

205850

AF XY:

0.0123

show subpopulations

Gnomad AFR exome

AF:

0.0107

Gnomad AMR exome

AF:

0.0116

Gnomad ASJ exome

AF:

0.00970

Gnomad EAS exome

AF:

0.000126

Gnomad FIN exome

AF:

0.00932

Gnomad NFE exome

AF:

0.0168

Gnomad OTH exome

AF:

0.0177

GnomAD4 exome

AF:

0.0164

AC:

23045

AN:

1404124

Hom.:

260

Cov.:

AF XY:

0.0160

AC XY:

11141

AN XY:

695524

show subpopulations

African (AFR)

AF:

0.0100

AC:

327

AN:

32538

American (AMR)

AF:

0.0119

AC:

480

AN:

40426

Ashkenazi Jewish (ASJ)

AF:

0.0105

AC:

250

AN:

23724

East Asian (EAS)

AF:

0.0000799

AC:

AN:

37536

South Asian (SAS)

AF:

0.00593

AC:

482

AN:

81246

European-Finnish (FIN)

AF:

0.00837

AC:

387

AN:

46250

Middle Eastern (MID)

AF:

0.0252

AC:

127

AN:

5034

European-Non Finnish (NFE)

AF:

0.0185

AC:

19965

AN:

1079670

Other (OTH)

AF:

0.0177

AC:

1024

AN:

57700

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.521

Heterozygous variant carriers

937

1874

2812

3749

4686

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

742

1484

2226

2968

3710

<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:

0.0146

AC:

2119

AN:

144746

Hom.:

Cov.:

AF XY:

0.0135

AC XY:

951

AN XY:

70242

show subpopulations

African (AFR)

AF:

0.0125

AC:

491

AN:

39380

American (AMR)

AF:

0.0162

AC:

223

AN:

13784

Ashkenazi Jewish (ASJ)

AF:

0.00789

AC:

AN:

3420

East Asian (EAS)

AF:

0.00

AC:

AN:

4924

South Asian (SAS)

AF:

0.00432

AC:

AN:

4396

European-Finnish (FIN)

AF:

0.00801

AC:

AN:

9610

Middle Eastern (MID)

AF:

0.0211

AC:

AN:

284

European-Non Finnish (NFE)

AF:

0.0186

AC:

1232

AN:

66088

Other (OTH)

AF:

0.0172

AC:

AN:

1974

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.529

Heterozygous variant carriers

190

285

380

475

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

<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:

0.0109

Hom.:

Bravo

AF:

0.0149

Asia WGS

AF:

0.00202

AC:

AN:

3476

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:5

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Primary ciliary dyskinesia

Uncertain:1Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 01, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

9102+8G>A in intron 55 of DNAH11: This variant is not expected to have clinical significance because it is not located within the conserved splice consensus seq uence. It has been identified in 1.8% (155/8422) of European American chromosome s from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.w ashington.edu/EVS; dbSNP rs72657374). -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Primary ciliary dyskinesia 7

Benign:1

Oct 03, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Sep 06, 2019

GeneDx

Significance:Likely 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

-0.70

CADD

Benign

2.0

(source)

DANN

Benign

0.80

PhyloP100

-0.15

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00013

dbscSNV1_RF

Benign

0.0020

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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