rs76229167

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.2683G>A(p.Glu895Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00305 in 1,612,148 control chromosomes in the GnomAD database, including 136 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.015 ( 64 hom., cov: 31)

Exomes 𝑓: 0.0018 ( 72 hom. )

Consequence

DNAH5
NM_001369.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: 1.05

Publications

6 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:

DNAH5-AS1 (HGNC:40187):

DNAH5-AS1 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=0.002672851).

BP6

Variant 5-13886024-C-T is Benign according to our data. Variant chr5-13886024-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 163156.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0501 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.2683G>A	p.Glu895Lys	missense	Exon 18 of 79	NP_001360.1	Q8TE73
	DNAH5-AS1	NR_199035.1		n.118-10565C>T		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DNAH5	ENST00000265104.5	TSL:1 MANE Select	c.2683G>A	p.Glu895Lys	missense	Exon 18 of 79	ENSP00000265104.4	Q8TE73
DNAH5	ENST00000681290.1		c.2638G>A	p.Glu880Lys	missense	Exon 18 of 79	ENSP00000505288.1	A0A7P0Z455
DNAH5-AS1	ENST00000503244.2	TSL:4	n.254-10565C>T		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0153

AC:

2313

AN:

151182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0517

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00907

Gnomad ASJ

AF:

0.00260

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00968

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.0130

GnomAD2 exomes

AF:

0.00415

AC:

1041

AN:

250768

AF XY:

0.00325

show subpopulations

Gnomad AFR exome

AF:

0.0533

Gnomad AMR exome

AF:

0.00295

Gnomad ASJ exome

AF:

0.00278

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000203

Gnomad OTH exome

AF:

0.00310

GnomAD4 exome

AF:

0.00178

AC:

2594

AN:

1460846

Hom.:

Cov.:

AF XY:

0.00153

AC XY:

1110

AN XY:

726704

show subpopulations

African (AFR)

AF:

0.0559

AC:

1870

AN:

33468

American (AMR)

AF:

0.00304

AC:

136

AN:

44704

Ashkenazi Jewish (ASJ)

AF:

0.00314

AC:

AN:

26126

East Asian (EAS)

AF:

0.00

AC:

AN:

39664

South Asian (SAS)

AF:

0.000104

AC:

AN:

86194

European-Finnish (FIN)

AF:

0.0000378

AC:

AN:

52862

Middle Eastern (MID)

AF:

0.00451

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000157

AC:

175

AN:

1111690

Other (OTH)

AF:

0.00487

AC:

294

AN:

60370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

126

252

378

504

630

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

128

192

256

320

<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:

0.0154

AC:

2327

AN:

151302

Hom.:

Cov.:

AF XY:

0.0151

AC XY:

1114

AN XY:

73874

show subpopulations

African (AFR)

AF:

0.0519

AC:

2138

AN:

41182

American (AMR)

AF:

0.00906

AC:

137

AN:

15124

Ashkenazi Jewish (ASJ)

AF:

0.00260

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5134

South Asian (SAS)

AF:

0.00

AC:

AN:

4798

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10370

Middle Eastern (MID)

AF:

0.0104

AC:

AN:

288

European-Non Finnish (NFE)

AF:

0.000191

AC:

AN:

67932

Other (OTH)

AF:

0.0129

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

109

218

327

436

545

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

130

<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:

0.00593

Hom.:

Bravo

AF:

0.0177

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.0461

AC:

203

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.00490

AC:

595

Asia WGS

AF:

0.00491

AC:

AN:

3478

EpiCase

AF:

0.000273

EpiControl

AF:

0.000178

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Primary ciliary dyskinesia (3)

Primary ciliary dyskinesia 3 (3)

not provided (2)

not specified (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.057

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.80

CADD

Benign

9.8

(source)

DANN

Benign

0.46

DEOGEN2

Benign

0.039

Eigen

Benign

-0.91

Eigen_PC

Benign

-0.77

FATHMM_MKL

Benign

0.043

LIST_S2

Benign

0.26

MetaRNN

Benign

0.0027

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-0.29

PhyloP100

1.1

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.24

REVEL

Benign

0.016

Sift

Benign

0.77

Polyphen

0.0

Vest4

0.16

MVP

0.24

MPC

0.11

ClinPred

0.0017

GERP RS

3.0

Varity_R

0.029

gMVP

0.16

Mutation Taster

=99/1

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over