rs11868065

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_173628.4(DNAH17):c.3087G>A(p.Pro1029Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.519 in 1,609,368 control chromosomes in the GnomAD database, including 217,936 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.51 ( 19943 hom., cov: 31)

Exomes 𝑓: 0.52 ( 197993 hom. )

Consequence

DNAH17
NM_173628.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -6.21

Publications

12 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 17-78532509-C-T is Benign according to our data. Variant chr17-78532509-C-T is described in ClinVar as Benign. ClinVar VariationId is 402696.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-6.2 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.538 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH17	NM_173628.4 link	c.3087G>A	p.Pro1029Pro	synonymous_variant	Exon 20 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.3087G>A	p.Pro1029Pro	synonymous_variant	Exon 20 of 81	5	NM_173628.4	ENSP00000374490.6		Q9UFH2-1

Frequencies

GnomAD3 genomes

AF:

0.509

AC:

77319

AN:

151862

Hom.:

19934

Cov.:

show subpopulations

Gnomad AFR

AF:

0.489

Gnomad AMI

AF:

0.752

Gnomad AMR

AF:

0.438

Gnomad ASJ

AF:

0.517

Gnomad EAS

AF:

0.429

Gnomad SAS

AF:

0.437

Gnomad FIN

AF:

0.524

Gnomad MID

AF:

0.532

Gnomad NFE

AF:

0.542

Gnomad OTH

AF:

0.521

GnomAD2 exomes

AF:

0.492

AC:

119418

AN:

242860

AF XY:

0.497

show subpopulations

Gnomad AFR exome

AF:

0.481

Gnomad AMR exome

AF:

0.379

Gnomad ASJ exome

AF:

0.531

Gnomad EAS exome

AF:

0.430

Gnomad FIN exome

AF:

0.519

Gnomad NFE exome

AF:

0.542

Gnomad OTH exome

AF:

0.517

GnomAD4 exome

AF:

0.520

AC:

757622

AN:

1457388

Hom.:

197993

Cov.:

AF XY:

0.519

AC XY:

375851

AN XY:

724668

show subpopulations

African (AFR)

AF:

0.483

AC:

16144

AN:

33420

American (AMR)

AF:

0.386

AC:

17053

AN:

44186

Ashkenazi Jewish (ASJ)

AF:

0.530

AC:

13790

AN:

26024

East Asian (EAS)

AF:

0.440

AC:

17427

AN:

39620

South Asian (SAS)

AF:

0.447

AC:

38238

AN:

85524

European-Finnish (FIN)

AF:

0.524

AC:

27835

AN:

53076

Middle Eastern (MID)

AF:

0.555

AC:

2831

AN:

5098

European-Non Finnish (NFE)

AF:

0.534

AC:

593103

AN:

1110256

Other (OTH)

AF:

0.518

AC:

31201

AN:

60184

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

19905

39810

59715

79620

99525

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16764

33528

50292

67056

83820

<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:

0.509

AC:

77360

AN:

151980

Hom.:

19943

Cov.:

AF XY:

0.505

AC XY:

37499

AN XY:

74262

show subpopulations

African (AFR)

AF:

0.489

AC:

20252

AN:

41426

American (AMR)

AF:

0.437

AC:

6678

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.517

AC:

1793

AN:

3468

East Asian (EAS)

AF:

0.430

AC:

2222

AN:

5172

South Asian (SAS)

AF:

0.437

AC:

2104

AN:

4812

European-Finnish (FIN)

AF:

0.524

AC:

5537

AN:

10568

Middle Eastern (MID)

AF:

0.537

AC:

158

AN:

294

European-Non Finnish (NFE)

AF:

0.542

AC:

36836

AN:

67936

Other (OTH)

AF:

0.518

AC:

1097

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1922

3843

5765

7686

9608

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

690

1380

2070

2760

3450

<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:

0.530

Hom.:

10792

Bravo

AF:

0.501

Asia WGS

AF:

0.431

AC:

1499

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

May 04, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

-0.80

CADD

Benign

0.063

(source)

DANN

Benign

0.74

PhyloP100

-6.2

Mutation Taster

=96/4

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