rs9896398

Variant names:

Variant summary

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

The NM_173628.4(DNAH17):c.4531A>G(p.Thr1511Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.607 in 1,613,342 control chromosomes in the GnomAD database, including 301,130 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T1511I) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.62 ( 30346 hom., cov: 34)

Exomes 𝑓: 0.61 ( 270784 hom. )

Consequence

DNAH17
NM_173628.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.117

Publications

27 publications found

Variant links:

Genes affected

DNAH17 (HGNC:2946): (dynein axonemal heavy chain 17) Dyneins are microtubule-associated motor protein complexes composed of several heavy, light, and intermediate chains. DNAH17 is a heavy chain associated with axonemal dynein (Milisav and Affara, 1998 [PubMed 9545504]).[supplied by OMIM, Mar 2008]

DNAH17 Gene-Disease associations (from GenCC):

spermatogenic failure 39
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
non-syndromic male infertility due to sperm motility disorder
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

DNAH17 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=7.406597E-7).

BP6

Variant 17-78507511-T-C is Benign according to our data. Variant chr17-78507511-T-C is described in ClinVar as Benign. ClinVar VariationId is 402690.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.728 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH17	NM_173628.4 link	c.4531A>G	p.Thr1511Ala	missense_variant	Exon 28 of 81	ENST00000389840.7	NP_775899.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH17	ENST00000389840.7 link	c.4531A>G	p.Thr1511Ala	missense_variant	Exon 28 of 81	5	NM_173628.4	ENSP00000374490.6
DNAH17	ENST00000587177.1 link	n.583A>G		non_coding_transcript_exon_variant	Exon 2 of 7	5

Frequencies

GnomAD3 genomes

AF:

0.624

AC:

94855

AN:

152032

Hom.:

30319

Cov.:

show subpopulations

Gnomad AFR

AF:

0.734

Gnomad AMI

AF:

0.620

Gnomad AMR

AF:

0.478

Gnomad ASJ

AF:

0.646

Gnomad EAS

AF:

0.466

Gnomad SAS

AF:

0.535

Gnomad FIN

AF:

0.557

Gnomad MID

AF:

0.650

Gnomad NFE

AF:

0.617

Gnomad OTH

AF:

0.631

GnomAD2 exomes

AF:

0.563

AC:

140036

AN:

248814

AF XY:

0.568

show subpopulations

Gnomad AFR exome

AF:

0.732

Gnomad AMR exome

AF:

0.359

Gnomad ASJ exome

AF:

0.650

Gnomad EAS exome

AF:

0.463

Gnomad FIN exome

AF:

0.567

Gnomad NFE exome

AF:

0.615

Gnomad OTH exome

AF:

0.589

GnomAD4 exome

AF:

0.605

AC:

884358

AN:

1461192

Hom.:

270784

Cov.:

AF XY:

0.603

AC XY:

438577

AN XY:

726794

show subpopulations

African (AFR)

AF:

0.737

AC:

24685

AN:

33478

American (AMR)

AF:

0.374

AC:

16715

AN:

44690

Ashkenazi Jewish (ASJ)

AF:

0.648

AC:

16925

AN:

26136

East Asian (EAS)

AF:

0.477

AC:

18911

AN:

39680

South Asian (SAS)

AF:

0.539

AC:

46510

AN:

86248

European-Finnish (FIN)

AF:

0.568

AC:

30324

AN:

53378

Middle Eastern (MID)

AF:

0.649

AC:

3743

AN:

5766

European-Non Finnish (NFE)

AF:

0.620

AC:

689471

AN:

1111454

Other (OTH)

AF:

0.614

AC:

37074

AN:

60362

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

22468

44937

67405

89874

112342

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18432

36864

55296

73728

92160

<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:

0.624

AC:

94929

AN:

152150

Hom.:

30346

Cov.:

AF XY:

0.617

AC XY:

45870

AN XY:

74360

show subpopulations

African (AFR)

AF:

0.735

AC:

30490

AN:

41504

American (AMR)

AF:

0.478

AC:

7308

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.646

AC:

2242

AN:

3470

East Asian (EAS)

AF:

0.466

AC:

2409

AN:

5172

South Asian (SAS)

AF:

0.533

AC:

2573

AN:

4824

European-Finnish (FIN)

AF:

0.557

AC:

5889

AN:

10580

Middle Eastern (MID)

AF:

0.637

AC:

186

AN:

292

European-Non Finnish (NFE)

AF:

0.617

AC:

41943

AN:

67992

Other (OTH)

AF:

0.626

AC:

1324

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1824

3647

5471

7294

9118

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

758

1516

2274

3032

3790

<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:

0.621

Hom.:

97223

Bravo

AF:

0.623

TwinsUK

AF:

0.619

AC:

2294

ALSPAC

AF:

0.625

AC:

2408

ESP6500AA

AF:

0.736

AC:

3068

ESP6500EA

AF:

0.614

AC:

5214

ExAC

AF:

0.573

AC:

69344

Asia WGS

AF:

0.540

AC:

1881

AN:

3478

EpiCase

AF:

0.619

EpiControl

AF:

0.621

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

May 04, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

not specified

Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency

DNAH17-related disorder

Benign:1

Oct 17, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.056

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.70

CADD

Benign

0.24

(source)

DANN

Benign

0.39

DEOGEN2

Benign

0.0

.;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.027

LIST_S2

Benign

0.44

T;T

MetaRNN

Benign

7.4e-7

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.0

.;.

PhyloP100

0.12

PrimateAI

Benign

0.36

PROVEAN

Benign

0.0

.;.

REVEL

Benign

0.0

Sift

Pathogenic

0.0

.;.

Sift4G

Pathogenic

0.0

.;.

Vest4

0.014

ClinPred

0.00030

GERP RS

1.6

Varity_R

0.050

gMVP

0.11

Mutation Taster

=100/0

polymorphism (auto)

(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