chr17-78475284-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_173628.4(DNAH17):c.8505C>T(p.Asp2835Asp) variant causes a synonymous change. The variant allele was found at a frequency of 0.123 in 1,613,812 control chromosomes in the GnomAD database, including 13,092 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 1129 hom., cov: 32)

Exomes 𝑓: 0.12 ( 11963 hom. )

Consequence

DNAH17
NM_173628.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 4.10

Publications

11 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 -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.45).

BP6

Variant 17-78475284-G-A is Benign according to our data. Variant chr17-78475284-G-A is described in CliVar as Benign. Clinvar id is 402678.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-78475284-G-A is described in CliVar as Benign. Clinvar id is 402678.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.18 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH17	NM_173628.4 link	c.8505C>T	p.Asp2835Asp	synonymous_variant	Exon 54 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.8505C>T	p.Asp2835Asp	synonymous_variant	Exon 54 of 81	5	NM_173628.4	ENSP00000374490.6		Q9UFH2-1
DNAH17	ENST00000586052.5 link	n.1887C>T		non_coding_transcript_exon_variant	Exon 10 of 35	5

Frequencies

GnomAD3 genomes

AF:

0.116

AC:

17638

AN:

152132

Hom.:

1123

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0867

Gnomad AMI

AF:

0.138

Gnomad AMR

AF:

0.0993

Gnomad ASJ

AF:

0.115

Gnomad EAS

AF:

0.190

Gnomad SAS

AF:

0.180

Gnomad FIN

AF:

0.161

Gnomad MID

AF:

0.114

Gnomad NFE

AF:

0.120

Gnomad OTH

AF:

0.119

GnomAD2 exomes

AF:

0.130

AC:

32432

AN:

248784

AF XY:

0.136

show subpopulations

Gnomad AFR exome

AF:

0.0835

Gnomad AMR exome

AF:

0.0749

Gnomad ASJ exome

AF:

0.106

Gnomad EAS exome

AF:

0.195

Gnomad FIN exome

AF:

0.159

Gnomad NFE exome

AF:

0.125

Gnomad OTH exome

AF:

0.135

GnomAD4 exome

AF:

0.124

AC:

181214

AN:

1461562

Hom.:

11963

Cov.:

AF XY:

0.126

AC XY:

91705

AN XY:

727062

show subpopulations

African (AFR)

AF:

0.0821

AC:

2750

AN:

33480

American (AMR)

AF:

0.0772

AC:

3454

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.109

AC:

2854

AN:

26136

East Asian (EAS)

AF:

0.157

AC:

6221

AN:

39698

South Asian (SAS)

AF:

0.186

AC:

16029

AN:

86248

European-Finnish (FIN)

AF:

0.159

AC:

8509

AN:

53378

Middle Eastern (MID)

AF:

0.125

AC:

720

AN:

5768

European-Non Finnish (NFE)

AF:

0.120

AC:

132914

AN:

1111774

Other (OTH)

AF:

0.129

AC:

7763

AN:

60368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

8715

17431

26146

34862

43577

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4848

9696

14544

19392

24240

<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:

0.116

AC:

17660

AN:

152250

Hom.:

1129

Cov.:

AF XY:

0.119

AC XY:

8844

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.0871

AC:

3619

AN:

41550

American (AMR)

AF:

0.0990

AC:

1514

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.115

AC:

399

AN:

3472

East Asian (EAS)

AF:

0.190

AC:

981

AN:

5172

South Asian (SAS)

AF:

0.180

AC:

869

AN:

4824

European-Finnish (FIN)

AF:

0.161

AC:

1709

AN:

10598

Middle Eastern (MID)

AF:

0.112

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.120

AC:

8151

AN:

68014

Other (OTH)

AF:

0.122

AC:

259

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

795

1591

2386

3182

3977

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

208

416

624

832

1040

<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:

0.118

Hom.:

709

Bravo

AF:

0.108

Asia WGS

AF:

0.201

AC:

700

AN:

3478

EpiCase

AF:

0.124

EpiControl

AF:

0.128

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 28, 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

-0.45

CADD

Benign

8.6

(source)

DANN

Benign

0.91

PhyloP100

4.1

Mutation Taster

=93/7

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