rs140690090

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4BP6

The NM_001369.3(DNAH5):c.6407C>T(p.Thr2136Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000991 in 1,614,042 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. T2136T) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00010 ( 0 hom. )

Consequence

DNAH5
NM_001369.3 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:1

Conservation

PhyloP100: 5.04

Publications

2 publications found

Variant links:

Genes affected

DNAH5 (HGNC:2950): (dynein axonemal heavy chain 5) This gene encodes a dynein protein, which is part of a microtubule-associated motor protein complex consisting of heavy, light, and intermediate chains. This protein is an axonemal heavy chain dynein. It functions as a force-generating protein with ATPase activity, whereby the release of ADP is thought to produce the force-producing power stroke. Mutations in this gene cause primary ciliary dyskinesia type 3, as well as Kartagener syndrome, which are both diseases due to ciliary defects. [provided by RefSeq, Oct 2009]

DNAH5 Gene-Disease associations (from GenCC):

primary ciliary dyskinesia 3
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P, ClinGen
primary ciliary dyskinesia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

DNAH5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.39447832).

BP6

Variant 5-13829547-G-A is Benign according to our data. Variant chr5-13829547-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 454792.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH5	NM_001369.3 link	c.6407C>T	p.Thr2136Met	missense_variant	Exon 38 of 79	ENST00000265104.5	NP_001360.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
DNAH5	ENST00000265104.5 link	c.6407C>T	p.Thr2136Met	missense_variant	Exon 38 of 79	1	NM_001369.3	ENSP00000265104.4
DNAH5	ENST00000681290.1 link	c.6362C>T	p.Thr2121Met	missense_variant	Exon 38 of 79			ENSP00000505288.1
DNAH5	ENST00000683090.1 link	n.1338C>T		non_coding_transcript_exon_variant	Exon 3 of 7

Frequencies

GnomAD3 genomes

AF:

0.0000789

AC:

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.000955

GnomAD2 exomes

AF:

0.000151

AC:

AN:

251274

AF XY:

0.000147

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000434

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000150

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000101

AC:

148

AN:

1461860

Hom.:

Cov.:

AF XY:

0.000106

AC XY:

AN XY:

727230

show subpopulations

African (AFR)

AF:

0.000119

AC:

AN:

33478

American (AMR)

AF:

0.000358

AC:

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39694

South Asian (SAS)

AF:

0.000278

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.000520

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000737

AC:

AN:

1111994

Other (OTH)

AF:

0.000281

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

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:

0.0000789

AC:

AN:

152182

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74346

show subpopulations

African (AFR)

AF:

0.0000724

AC:

AN:

41448

American (AMR)

AF:

0.000196

AC:

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

68032

Other (OTH)

AF:

0.000955

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

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:

0.000217

Hom.:

Bravo

AF:

0.000132

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000157

AC:

Asia WGS

AF:

0.000867

AC:

AN:

3476

EpiCase

AF:

0.000164

EpiControl

AF:

0.000474

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:2Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Primary ciliary dyskinesia

Uncertain:1Benign:1

Oct 22, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Oct 28, 2019

Natera, Inc.

Significance:Uncertain significance

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Primary ciliary dyskinesia 3

Uncertain:1

Jul 08, 2021

Fulgent Genetics, Fulgent Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.15

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.29

Eigen

Uncertain

0.64

Eigen_PC

Uncertain

0.66

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.84

M_CAP

Benign

0.038

MetaRNN

Benign

0.39

MetaSVM

Benign

-0.78

MutationAssessor

Uncertain

2.4

PhyloP100

5.0

PrimateAI

Uncertain

0.76

PROVEAN

Uncertain

-4.1

REVEL

Benign

0.22

Sift

Uncertain

0.024

Polyphen

0.99

Vest4

0.39

MVP

0.75

MPC

0.47

ClinPred

0.66

GERP RS

5.6

Varity_R

0.21

gMVP

0.66

Mutation Taster

=24/76

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over