chr5-13944403-A-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001369.3(DNAH5):c.36T>G(p.His12Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.938 in 1,613,616 control chromosomes in the GnomAD database, including 710,864 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.93 ( 65399 hom., cov: 31)

Exomes 𝑓: 0.94 ( 645465 hom. )

Consequence

DNAH5
NM_001369.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:12

Conservation

PhyloP100: 0.762

Publications

31 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: G2P, ClinGen, Labcorp Genetics (formerly Invitae)
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: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=5.602909E-7).

BP6

Variant 5-13944403-A-C is Benign according to our data. Variant chr5-13944403-A-C is described in ClinVar as Benign. ClinVar VariationId is 178760.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.936 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001369.3. 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
	DNAH5	NM_001369.3	MANE Select	c.36T>G	p.His12Gln	missense	Exon 1 of 79	NP_001360.1	Q8TE73

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH5	ENST00000265104.5	TSL:1 MANE Select	c.36T>G	p.His12Gln	missense	Exon 1 of 79	ENSP00000265104.4	Q8TE73
	DNAH5	ENST00000681290.1		c.13-13159T>G		intron	N/A	ENSP00000505288.1	A0A7P0Z455

Frequencies

GnomAD3 genomes

AF:

0.926

AC:

140894

AN:

152092

Hom.:

65356

Cov.:

show subpopulations

Gnomad AFR

AF:

0.886

Gnomad AMI

AF:

0.998

Gnomad AMR

AF:

0.936

Gnomad ASJ

AF:

0.957

Gnomad EAS

AF:

0.886

Gnomad SAS

AF:

0.919

Gnomad FIN

AF:

0.979

Gnomad MID

AF:

0.858

Gnomad NFE

AF:

0.942

Gnomad OTH

AF:

0.924

GnomAD2 exomes

AF:

0.936

AC:

234735

AN:

250786

AF XY:

0.935

show subpopulations

Gnomad AFR exome

AF:

0.884

Gnomad AMR exome

AF:

0.956

Gnomad ASJ exome

AF:

0.953

Gnomad EAS exome

AF:

0.881

Gnomad FIN exome

AF:

0.977

Gnomad NFE exome

AF:

0.942

Gnomad OTH exome

AF:

0.930

GnomAD4 exome

AF:

0.940

AC:

1373106

AN:

1461406

Hom.:

645465

Cov.:

AF XY:

0.939

AC XY:

682495

AN XY:

727044

show subpopulations

African (AFR)

AF:

0.881

AC:

29499

AN:

33468

American (AMR)

AF:

0.954

AC:

42637

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.953

AC:

24912

AN:

26132

East Asian (EAS)

AF:

0.900

AC:

35718

AN:

39688

South Asian (SAS)

AF:

0.914

AC:

78869

AN:

86254

European-Finnish (FIN)

AF:

0.978

AC:

51998

AN:

53180

Middle Eastern (MID)

AF:

0.862

AC:

4968

AN:

5766

European-Non Finnish (NFE)

AF:

0.943

AC:

1048494

AN:

1111820

Other (OTH)

AF:

0.928

AC:

56011

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

4397

8794

13190

17587

21984

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21588

43176

64764

86352

107940

<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:

0.926

AC:

140995

AN:

152210

Hom.:

65399

Cov.:

AF XY:

0.927

AC XY:

69016

AN XY:

74420

show subpopulations

African (AFR)

AF:

0.885

AC:

36753

AN:

41512

American (AMR)

AF:

0.936

AC:

14312

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.957

AC:

3321

AN:

3470

East Asian (EAS)

AF:

0.886

AC:

4577

AN:

5168

South Asian (SAS)

AF:

0.918

AC:

4424

AN:

4820

European-Finnish (FIN)

AF:

0.979

AC:

10387

AN:

10610

Middle Eastern (MID)

AF:

0.861

AC:

253

AN:

294

European-Non Finnish (NFE)

AF:

0.942

AC:

64101

AN:

68024

Other (OTH)

AF:

0.925

AC:

1957

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

506

1012

1517

2023

2529

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

908

1816

2724

3632

4540

<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:

0.933

Hom.:

229160

Bravo

AF:

0.922

TwinsUK

AF:

0.947

AC:

3511

ALSPAC

AF:

0.948

AC:

3652

ESP6500AA

AF:

0.894

AC:

3937

ESP6500EA

AF:

0.942

AC:

8101

ExAC

AF:

0.936

AC:

113608

Asia WGS

AF:

0.907

AC:

3154

AN:

3478

EpiCase

AF:

0.934

EpiControl

AF:

0.935

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (4)

Primary ciliary dyskinesia (3)

Primary ciliary dyskinesia 3 (3)

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.056

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.74

CADD

Benign

(source)

DANN

Benign

0.63

DEOGEN2

Benign

0.027

Eigen

Benign

-0.87

Eigen_PC

Benign

-0.56

FATHMM_MKL

Benign

0.033

LIST_S2

Benign

0.14

MetaRNN

Benign

5.6e-7

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-2.1

PhyloP100

0.76

PrimateAI

Uncertain

0.53

PROVEAN

Benign

1.3

REVEL

Benign

0.091

Sift

Benign

1.0

Polyphen

0.0

Vest4

0.041

MutPred

0.077

Gain of helix (P = 0.0425)

MPC

0.094

ClinPred

0.0062

GERP RS

3.8

PromoterAI

0.013

Neutral

(source)

Varity_R

0.053

gMVP

0.14

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over