rs200466467

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM1BP4_Moderate

The NM_001277115.2(DNAH11):c.13309C>T(p.Arg4437Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000172 in 1,591,692 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R4437H) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00031 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00016 ( 0 hom. )

Consequence

DNAH11
NM_001277115.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.181

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 links:

CDCA7L (HGNC:30777): (cell division cycle associated 7 like) Acts upstream of or within positive regulation of cell population proliferation. Located in cytosol; fibrillar center; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

CDCA7L links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM1

In a hotspot region, there are 3 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 0 benign, 9 uncertain in NM_001277115.2

BP4

Computational evidence support a benign effect (MetaRNN=0.099295855).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DNAH11	NM_001277115.2	MANE Select	c.13309C>T	p.Arg4437Cys	missense	Exon 82 of 82	NP_001264044.1	Q96DT5
CDCA7L	NM_018719.5	MANE Select	c.*1310G>A		3_prime_UTR	Exon 10 of 10	NP_061189.2
CDCA7L	NM_001127370.3		c.*1310G>A		3_prime_UTR	Exon 11 of 11	NP_001120842.1	Q96GN5-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DNAH11	ENST00000409508.8	TSL:5 MANE Select	c.13309C>T	p.Arg4437Cys	missense	Exon 82 of 82	ENSP00000475939.1	Q96DT5
CDCA7L	ENST00000406877.8	TSL:1 MANE Select	c.*1310G>A		3_prime_UTR	Exon 10 of 10	ENSP00000383986.3	Q96GN5-1
CDCA7L	ENST00000934293.1		c.*1310G>A		3_prime_UTR	Exon 10 of 10	ENSP00000604352.1

Frequencies

GnomAD3 genomes

AF:

0.000302

AC:

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000555

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00173

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000354

AC:

AN:

234432

AF XY:

0.000354

show subpopulations

Gnomad AFR exome

AF:

0.000921

Gnomad AMR exome

AF:

0.000195

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00161

Gnomad FIN exome

AF:

0.0000475

Gnomad NFE exome

AF:

0.000185

Gnomad OTH exome

AF:

0.000359

GnomAD4 exome

AF:

0.000158

AC:

227

AN:

1439400

Hom.:

Cov.:

AF XY:

0.000160

AC XY:

114

AN XY:

713810

show subpopulations

African (AFR)

AF:

0.000860

AC:

AN:

32572

American (AMR)

AF:

0.000195

AC:

AN:

40988

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24996

East Asian (EAS)

AF:

0.000915

AC:

AN:

39334

South Asian (SAS)

AF:

0.000363

AC:

AN:

82756

European-Finnish (FIN)

AF:

0.0000189

AC:

AN:

53014

Middle Eastern (MID)

AF:

0.000177

AC:

AN:

5654

European-Non Finnish (NFE)

AF:

0.0000945

AC:

104

AN:

1100714

Other (OTH)

AF:

0.000320

AC:

AN:

59372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.000309

AC:

AN:

152292

Hom.:

Cov.:

AF XY:

0.000228

AC XY:

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.000577

AC:

AN:

41584

American (AMR)

AF:

0.000196

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00174

AC:

AN:

5178

South Asian (SAS)

AF:

0.000414

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10600

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000132

AC:

AN:

68016

Other (OTH)

AF:

0.00

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

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:

0.000245

Hom.:

Bravo

AF:

0.000344

ESP6500AA

AF:

0.000797

AC:

ESP6500EA

AF:

0.000122

AC:

ExAC

AF:

0.000356

AC:

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Primary ciliary dyskinesia (3)

Primary ciliary dyskinesia 7 (2)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.31

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.31

Eigen

Benign

-0.59

Eigen_PC

Benign

-0.85

FATHMM_MKL

Benign

0.28

LIST_S2

Uncertain

0.86

M_CAP

Benign

0.032

MetaRNN

Benign

0.099

MetaSVM

Benign

-0.99

PhyloP100

-0.18

PrimateAI

Benign

0.45

PROVEAN

Pathogenic

-6.1

REVEL

Benign

0.26

Sift

Benign

0.066

Vest4

0.60

MVP

0.18

ClinPred

0.18

GERP RS

-6.7

Varity_R

0.47

gMVP

0.58

Mutation Taster

=5/95

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