rs17729253

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.3834A>G(p.Leu1278Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.235 in 1,613,036 control chromosomes in the GnomAD database, including 47,292 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.19 ( 3595 hom., cov: 33)

Exomes 𝑓: 0.24 ( 43697 hom. )

Consequence

DNAH17
NM_173628.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.627

Publications

13 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=-0.57).

BP6

Variant 17-78525039-T-C is Benign according to our data. Variant chr17-78525039-T-C is described in ClinVar as Benign. ClinVar VariationId is 402692.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.627 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.26 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH17	NM_173628.4 link	c.3834A>G	p.Leu1278Leu	synonymous_variant	Exon 25 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.3834A>G	p.Leu1278Leu	synonymous_variant	Exon 25 of 81	5	NM_173628.4	ENSP00000374490.6		Q9UFH2-1

Frequencies

GnomAD3 genomes

AF:

0.193

AC:

29353

AN:

152106

Hom.:

3594

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0636

Gnomad AMI

AF:

0.357

Gnomad AMR

AF:

0.217

Gnomad ASJ

AF:

0.300

Gnomad EAS

AF:

0.0782

Gnomad SAS

AF:

0.220

Gnomad FIN

AF:

0.198

Gnomad MID

AF:

0.310

Gnomad NFE

AF:

0.263

Gnomad OTH

AF:

0.233

GnomAD2 exomes

AF:

0.222

AC:

55319

AN:

248668

AF XY:

0.229

show subpopulations

Gnomad AFR exome

AF:

0.0568

Gnomad AMR exome

AF:

0.206

Gnomad ASJ exome

AF:

0.310

Gnomad EAS exome

AF:

0.0822

Gnomad FIN exome

AF:

0.195

Gnomad NFE exome

AF:

0.266

Gnomad OTH exome

AF:

0.253

GnomAD4 exome

AF:

0.239

AC:

349636

AN:

1460812

Hom.:

43697

Cov.:

AF XY:

0.241

AC XY:

174839

AN XY:

726612

show subpopulations

African (AFR)

AF:

0.0553

AC:

1850

AN:

33478

American (AMR)

AF:

0.211

AC:

9428

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.311

AC:

8126

AN:

26126

East Asian (EAS)

AF:

0.0710

AC:

2820

AN:

39696

South Asian (SAS)

AF:

0.232

AC:

20013

AN:

86238

European-Finnish (FIN)

AF:

0.199

AC:

10580

AN:

53116

Middle Eastern (MID)

AF:

0.296

AC:

1706

AN:

5764

European-Non Finnish (NFE)

AF:

0.253

AC:

281106

AN:

1111342

Other (OTH)

AF:

0.232

AC:

14007

AN:

60340

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

15267

30533

45800

61066

76333

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9162

18324

27486

36648

45810

<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:

0.193

AC:

29353

AN:

152224

Hom.:

3595

Cov.:

AF XY:

0.190

AC XY:

14129

AN XY:

74448

show subpopulations

African (AFR)

AF:

0.0637

AC:

2647

AN:

41572

American (AMR)

AF:

0.217

AC:

3316

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.300

AC:

1041

AN:

3466

East Asian (EAS)

AF:

0.0782

AC:

405

AN:

5178

South Asian (SAS)

AF:

0.218

AC:

1055

AN:

4832

European-Finnish (FIN)

AF:

0.198

AC:

2098

AN:

10604

Middle Eastern (MID)

AF:

0.320

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.263

AC:

17885

AN:

67952

Other (OTH)

AF:

0.230

AC:

486

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1201

2402

3603

4804

6005

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

322

644

966

1288

1610

<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:

0.233

Hom.:

4812

Bravo

AF:

0.188

Asia WGS

AF:

0.129

AC:

451

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

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 29, 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

-0.57

CADD

Benign

9.6

(source)

DANN

Benign

0.76

PhyloP100

0.63

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