rs626439

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_173628.4(DNAH17):c.4500G>A(p.Glu1500Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.253 in 1,613,666 control chromosomes in the GnomAD database, including 55,734 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.25 ( 5201 hom., cov: 33)

Exomes 𝑓: 0.25 ( 50533 hom. )

Consequence

DNAH17
NM_173628.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.710

Publications

18 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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.42).

BP6

Variant 17-78507542-C-T is Benign according to our data. Variant chr17-78507542-C-T is described in ClinVar as Benign. ClinVar VariationId is 402691.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.71 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.451 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH17	NM_173628.4 link	c.4500G>A	p.Glu1500Glu	synonymous_variant	Exon 28 of 81	ENST00000389840.7	NP_775899.3	Q9UFH2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH17	ENST00000389840.7 link	c.4500G>A	p.Glu1500Glu	synonymous_variant	Exon 28 of 81	5	NM_173628.4	ENSP00000374490.6		Q9UFH2-1
DNAH17	ENST00000587177.1 link	n.552G>A		non_coding_transcript_exon_variant	Exon 2 of 7	5

Frequencies

GnomAD3 genomes

AF:

0.249

AC:

37842

AN:

152044

Hom.:

5192

Cov.:

show subpopulations

Gnomad AFR

AF:

0.187

Gnomad AMI

AF:

0.283

Gnomad AMR

AF:

0.377

Gnomad ASJ

AF:

0.192

Gnomad EAS

AF:

0.467

Gnomad SAS

AF:

0.377

Gnomad FIN

AF:

0.310

Gnomad MID

AF:

0.177

Gnomad NFE

AF:

0.226

Gnomad OTH

AF:

0.229

GnomAD2 exomes

AF:

0.300

AC:

74590

AN:

248720

AF XY:

0.295

show subpopulations

Gnomad AFR exome

AF:

0.191

Gnomad AMR exome

AF:

0.473

Gnomad ASJ exome

AF:

0.184

Gnomad EAS exome

AF:

0.470

Gnomad FIN exome

AF:

0.302

Gnomad NFE exome

AF:

0.227

Gnomad OTH exome

AF:

0.260

GnomAD4 exome

AF:

0.253

AC:

369876

AN:

1461504

Hom.:

50533

Cov.:

AF XY:

0.255

AC XY:

185674

AN XY:

727010

show subpopulations

African (AFR)

AF:

0.188

AC:

6294

AN:

33478

American (AMR)

AF:

0.459

AC:

20514

AN:

44684

Ashkenazi Jewish (ASJ)

AF:

0.187

AC:

4881

AN:

26136

East Asian (EAS)

AF:

0.465

AC:

18477

AN:

39700

South Asian (SAS)

AF:

0.370

AC:

31914

AN:

86248

European-Finnish (FIN)

AF:

0.301

AC:

16066

AN:

53358

Middle Eastern (MID)

AF:

0.194

AC:

1118

AN:

5766

European-Non Finnish (NFE)

AF:

0.230

AC:

255578

AN:

1111766

Other (OTH)

AF:

0.249

AC:

15034

AN:

60368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

17896

35793

53689

71586

89482

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9170

18340

27510

36680

45850

<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:

0.249

AC:

37880

AN:

152162

Hom.:

5201

Cov.:

AF XY:

0.259

AC XY:

19242

AN XY:

74376

show subpopulations

African (AFR)

AF:

0.187

AC:

7749

AN:

41532

American (AMR)

AF:

0.377

AC:

5768

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.192

AC:

665

AN:

3470

East Asian (EAS)

AF:

0.467

AC:

2412

AN:

5166

South Asian (SAS)

AF:

0.379

AC:

1827

AN:

4822

European-Finnish (FIN)

AF:

0.310

AC:

3281

AN:

10572

Middle Eastern (MID)

AF:

0.184

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.226

AC:

15369

AN:

68000

Other (OTH)

AF:

0.235

AC:

497

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1434

2867

4301

5734

7168

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

402

804

1206

1608

2010

<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:

0.232

Hom.:

6410

Bravo

AF:

0.251

Asia WGS

AF:

0.382

AC:

1325

AN:

3478

EpiCase

AF:

0.214

EpiControl

AF:

0.221

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

BayesDel_noAF

Benign

-0.42

CADD

Benign

8.5

(source)

DANN

Benign

0.68

PhyloP100

0.71

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