rs72657327

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 0P and 3B. BP4_ModerateBS1_Supporting

The NM_001277115.2(DNAH11):c.4775G>T(p.Cys1592Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000181 in 1,586,290 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C1592G) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00021 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00018 ( 1 hom. )

Consequence

DNAH11
NM_001277115.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:6

Conservation

PhyloP100: 2.03

Publications

6 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: Likely_benign. The variant received -3 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.11033535).

BS1

Variant frequency is greater than expected in population mid. GnomAdExome4 allele frequency = 0.000178 (255/1434002) while in subpopulation MID AF = 0.00436 (25/5730). AF 95% confidence interval is 0.00303. There are 1 homozygotes in GnomAdExome4. There are 136 alleles in the male GnomAdExome4 subpopulation. Median coverage is 29. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

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.4775G>T	p.Cys1592Phe	missense	Exon 27 of 82	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.4775G>T	p.Cys1592Phe	missense	Exon 27 of 82	ENSP00000475939.1	Q96DT5

Frequencies

GnomAD3 genomes

AF:

0.000210

AC:

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000309

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000198

AC:

AN:

207000

AF XY:

0.000217

show subpopulations

Gnomad AFR exome

AF:

0.0000818

Gnomad AMR exome

AF:

0.0000334

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000355

Gnomad OTH exome

AF:

0.000573

GnomAD4 exome

AF:

0.000178

AC:

255

AN:

1434002

Hom.:

Cov.:

AF XY:

0.000191

AC XY:

136

AN XY:

710246

show subpopulations

African (AFR)

AF:

0.0000911

AC:

AN:

32944

American (AMR)

AF:

0.0000733

AC:

AN:

40900

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25538

East Asian (EAS)

AF:

0.00

AC:

AN:

38728

South Asian (SAS)

AF:

0.000245

AC:

AN:

81550

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51870

Middle Eastern (MID)

AF:

0.00436

AC:

AN:

5730

European-Non Finnish (NFE)

AF:

0.000167

AC:

183

AN:

1097332

Other (OTH)

AF:

0.000353

AC:

AN:

59410

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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:

0.000210

AC:

AN:

152288

Hom.:

Cov.:

AF XY:

0.000188

AC XY:

AN XY:

74464

show subpopulations

African (AFR)

AF:

0.000168

AC:

AN:

41576

American (AMR)

AF:

0.000131

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.000208

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000309

AC:

AN:

68028

Other (OTH)

AF:

0.000473

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.523

Heterozygous variant carriers

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:

0.000262

Hom.:

Bravo

AF:

0.000185

ESP6500AA

AF:

0.000272

AC:

ESP6500EA

AF:

0.000979

AC:

ExAC

AF:

0.000191

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Primary ciliary dyskinesia 7 (4)

Primary ciliary dyskinesia (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.099

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.30

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.15

Eigen

Uncertain

0.51

Eigen_PC

Uncertain

0.57

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.79

M_CAP

Benign

0.046

MetaRNN

Benign

0.11

MetaSVM

Benign

-0.48

PhyloP100

2.0

PrimateAI

Benign

0.46

PROVEAN

Uncertain

-2.4

REVEL

Benign

0.13

Sift

Uncertain

0.0070

Vest4

0.50

MVP

0.49

ClinPred

0.084

GERP RS

6.0

Varity_R

0.49

gMVP

0.25

Mutation Taster

=6/94

disease causing

(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

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over