rs189821372

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 1P and 9B. PP3BP6BS1BS2

The NM_001277115.2(DNAH11):c.8798-5G>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 0.00412 in 1,590,046 control chromosomes in the GnomAD database, including 30 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0032 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0042 ( 27 hom. )

Consequence

DNAH11
NM_001277115.2 splice_region, intron

Scores

Splicing: ADA: 0.9741

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:4

Conservation

PhyloP100: 0.295

Publications

3 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: Labcorp Genetics (formerly Invitae), ClinGen, Laboratory for Molecular Medicine
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 -8 ACMG points.

PP3

Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: dbscSNV1_ADA, max_spliceai. No scorers claiming Uncertain. Scorers claiming Benign: dbscSNV1_RF.

BP6

Variant 7-21750217-G-A is Benign according to our data. Variant chr7-21750217-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 163114.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00316 (481/152138) while in subpopulation SAS AF = 0.0083 (40/4818). AF 95% confidence interval is 0.00627. There are 3 homozygotes in GnomAd4. There are 210 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 3 AD,AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001277115.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH11	NM_001277115.2	MANE Select	c.8798-5G>A		splice_region intron	N/A	NP_001264044.1	Q96DT5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH11	ENST00000409508.8	TSL:5 MANE Select	c.8798-5G>A		splice_region intron	N/A	ENSP00000475939.1	Q96DT5

Frequencies

GnomAD3 genomes

AF:

0.00317

AC:

482

AN:

152020

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000797

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00203

Gnomad ASJ

AF:

0.00952

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00850

Gnomad FIN

AF:

0.00104

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00472

Gnomad OTH

AF:

0.00480

GnomAD2 exomes

AF:

0.00391

AC:

868

AN:

221866

AF XY:

0.00420

show subpopulations

Gnomad AFR exome

AF:

0.000286

Gnomad AMR exome

AF:

0.00168

Gnomad ASJ exome

AF:

0.00819

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00227

Gnomad NFE exome

AF:

0.00416

Gnomad OTH exome

AF:

0.00453

GnomAD4 exome

AF:

0.00422

AC:

6069

AN:

1437908

Hom.:

Cov.:

AF XY:

0.00447

AC XY:

3188

AN XY:

712654

show subpopulations

African (AFR)

AF:

0.000733

AC:

AN:

32728

American (AMR)

AF:

0.00173

AC:

AN:

39962

Ashkenazi Jewish (ASJ)

AF:

0.00937

AC:

239

AN:

25500

East Asian (EAS)

AF:

0.0000255

AC:

AN:

39256

South Asian (SAS)

AF:

0.0102

AC:

811

AN:

79830

European-Finnish (FIN)

AF:

0.00265

AC:

140

AN:

52872

Middle Eastern (MID)

AF:

0.00472

AC:

AN:

5720

European-Non Finnish (NFE)

AF:

0.00408

AC:

4499

AN:

1102384

Other (OTH)

AF:

0.00434

AC:

259

AN:

59656

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

267

533

800

1066

1333

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

178

356

534

712

890

<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:

0.00316

AC:

481

AN:

152138

Hom.:

Cov.:

AF XY:

0.00282

AC XY:

210

AN XY:

74350

show subpopulations

African (AFR)

AF:

0.000795

AC:

AN:

41506

American (AMR)

AF:

0.00203

AC:

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.00952

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00830

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00104

AC:

AN:

10570

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00472

AC:

321

AN:

68006

Other (OTH)

AF:

0.00475

AC:

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

113

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00386

Hom.:

Bravo

AF:

0.00291

Asia WGS

AF:

0.00462

AC:

AN:

3476

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (2)

not provided (1)

Primary ciliary dyskinesia (1)

Primary ciliary dyskinesia 7 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

(source)

DANN

Benign

0.67

PhyloP100

0.29

Mutation Taster

=83/17

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

0.97

dbscSNV1_RF

Benign

0.68

SpliceAI score (max)

0.63

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.63

Position offset: 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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over