dbSNP rs368331: DNAH11:c.6273+554A>G (chr7-21703356-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001277115.2(DNAH11):c.6273+554A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0483 in 155,720 control chromosomes in the GnomAD database, including 269 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.048 ( 260 hom., cov: 32)

Exomes 𝑓: 0.055 ( 9 hom. )

Consequence

DNAH11
NM_001277115.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.169

Publications

10 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), Laboratory for Molecular Medicine, ClinGen
primary ciliary dyskinesia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

DNAH11 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_001277115.2, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.135 is higher than 0.05.

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.6273+554A>G		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.6273+554A>G		intron	N/A	ENSP00000475939.1	Q96DT5
	DNAH11	ENST00000465129.1	TSL:3	n.94-93A>G		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0482

AC:

7335

AN:

152148

Hom.:

262

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0109

Gnomad AMI

AF:

0.115

Gnomad AMR

AF:

0.0245

Gnomad ASJ

AF:

0.0490

Gnomad EAS

AF:

0.143

Gnomad SAS

AF:

0.0828

Gnomad FIN

AF:

0.0603

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0635

Gnomad OTH

AF:

0.0565

GnomAD4 exome

AF:

0.0553

AC:

191

AN:

3454

Hom.:

AF XY:

0.0629

AC XY:

115

AN XY:

1828

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.0278

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.0556

AC:

AN:

East Asian (EAS)

AF:

0.0667

AC:

AN:

South Asian (SAS)

AF:

0.0822

AC:

AN:

146

European-Finnish (FIN)

AF:

0.0652

AC:

AN:

138

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0538

AC:

150

AN:

2788

Other (OTH)

AF:

0.0654

AC:

AN:

214

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.520

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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

GnomAD4 genome

AF:

0.0482

AC:

7333

AN:

152266

Hom.:

260

Cov.:

AF XY:

0.0484

AC XY:

3606

AN XY:

74466

show subpopulations

African (AFR)

AF:

0.0108

AC:

450

AN:

41552

American (AMR)

AF:

0.0245

AC:

375

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0490

AC:

170

AN:

3472

East Asian (EAS)

AF:

0.144

AC:

743

AN:

5174

South Asian (SAS)

AF:

0.0831

AC:

401

AN:

4826

European-Finnish (FIN)

AF:

0.0603

AC:

640

AN:

10608

Middle Eastern (MID)

AF:

0.0408

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0635

AC:

4320

AN:

68016

Other (OTH)

AF:

0.0554

AC:

117

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

347

695

1042

1390

1737

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

200

300

400

500

<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:

0.0584

Hom.:

1324

Bravo

AF:

0.0443

Asia WGS

AF:

0.0910

AC:

316

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.37

(source)

DANN

Benign

0.54

PhyloP100

-0.17

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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