7-21748602-C-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS1

The NM_001277115.2(DNAH11):c.8533C>G(p.Arg2845Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00132 in 1,552,168 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 Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R2845Q) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0016 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0013 ( 0 hom. )

Consequence

DNAH11
NM_001277115.2 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:5B:2

Conservation

PhyloP100: 2.42

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: 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 -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007217258).

BP6

Variant 7-21748602-C-G is Benign according to our data. Variant chr7-21748602-C-G is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 359658.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00161 (245/152328) while in subpopulation AFR AF = 0.00322 (134/41574). AF 95% confidence interval is 0.00278. There are 1 homozygotes in GnomAd4. There are 111 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

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.8533C>G	p.Arg2845Gly	missense	Exon 52 of 82	NP_001264044.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH11	ENST00000409508.8	TSL:5 MANE Select	c.8533C>G	p.Arg2845Gly	missense	Exon 52 of 82	ENSP00000475939.1

Frequencies

GnomAD3 genomes

AF:

0.00160

AC:

243

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00318

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000282

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00126

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.00117

AC:

249

AN:

212646

AF XY:

0.00106

show subpopulations

Gnomad AFR exome

AF:

0.00294

Gnomad AMR exome

AF:

0.000909

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000195

Gnomad NFE exome

AF:

0.00164

Gnomad OTH exome

AF:

0.00184

GnomAD4 exome

AF:

0.00129

AC:

1800

AN:

1399840

Hom.:

Cov.:

AF XY:

0.00120

AC XY:

828

AN XY:

692040

show subpopulations

African (AFR)

AF:

0.00278

AC:

AN:

31250

American (AMR)

AF:

0.000870

AC:

AN:

36798

Ashkenazi Jewish (ASJ)

AF:

0.0000421

AC:

AN:

23750

East Asian (EAS)

AF:

0.00

AC:

AN:

37888

South Asian (SAS)

AF:

0.000329

AC:

AN:

75894

European-Finnish (FIN)

AF:

0.000462

AC:

AN:

51956

Middle Eastern (MID)

AF:

0.00418

AC:

AN:

5508

European-Non Finnish (NFE)

AF:

0.00140

AC:

1515

AN:

1079472

Other (OTH)

AF:

0.00162

AC:

AN:

57324

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

193

290

386

483

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

120

180

240

300

<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:

0.00161

AC:

245

AN:

152328

Hom.:

Cov.:

AF XY:

0.00149

AC XY:

111

AN XY:

74480

show subpopulations

African (AFR)

AF:

0.00322

AC:

134

AN:

41574

American (AMR)

AF:

0.00131

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.000282

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00126

AC:

AN:

68030

Other (OTH)

AF:

0.000473

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

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:

0.00125

Hom.:

Bravo

AF:

0.00168

TwinsUK

AF:

0.00243

AC:

ALSPAC

AF:

0.00182

AC:

ESP6500AA

AF:

0.00232

AC:

ESP6500EA

AF:

0.000966

AC:

ExAC

AF:

0.00126

AC:

152

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Primary ciliary dyskinesia (2)

Primary ciliary dyskinesia 7 (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.36

Eigen

Benign

-0.56

Eigen_PC

Benign

-0.53

FATHMM_MKL

Benign

0.33

LIST_S2

Uncertain

0.88

M_CAP

Benign

0.0062

MetaRNN

Benign

0.0072

MetaSVM

Benign

-1.1

PhyloP100

2.4

PrimateAI

Benign

0.25

PROVEAN

Uncertain

-2.9

REVEL

Benign

0.030

Sift

Uncertain

0.0020

Vest4

0.26

MVP

0.16

ClinPred

0.037

GERP RS

1.5

Varity_R

0.12

gMVP

0.40

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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