17-78425386-A-G

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.13101T>C(p.Pro4367Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 1,613,646 control chromosomes in the GnomAD database, including 23,050 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 2446 hom., cov: 32)

Exomes 𝑓: 0.16 ( 20604 hom. )

Consequence

DNAH17
NM_173628.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.23

Publications

15 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=-0.88).

BP6

Variant 17-78425386-A-G is Benign according to our data. Variant chr17-78425386-A-G is described in ClinVar as Benign. ClinVar VariationId is 402671.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.23 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.226 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH17	NM_173628.4 link	c.13101T>C	p.Pro4367Pro	synonymous_variant	Exon 80 of 81	ENST00000389840.7	NP_775899.3	Q9UFH2-1
DNAH17	XM_011525416.3 link	c.13113T>C	p.Pro4371Pro	synonymous_variant	Exon 80 of 81		XP_011523718.1
DNAH17	XM_024451013.2 link	c.12969T>C	p.Pro4323Pro	synonymous_variant	Exon 79 of 80		XP_024306781.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH17	ENST00000389840.7 link	c.13101T>C	p.Pro4367Pro	synonymous_variant	Exon 80 of 81	5	NM_173628.4	ENSP00000374490.6		Q9UFH2-1

Frequencies

GnomAD3 genomes

AF:

0.173

AC:

26294

AN:

151970

Hom.:

2443

Cov.:

show subpopulations

Gnomad AFR

AF:

0.230

Gnomad AMI

AF:

0.167

Gnomad AMR

AF:

0.130

Gnomad ASJ

AF:

0.231

Gnomad EAS

AF:

0.0306

Gnomad SAS

AF:

0.153

Gnomad FIN

AF:

0.111

Gnomad MID

AF:

0.206

Gnomad NFE

AF:

0.167

Gnomad OTH

AF:

0.179

GnomAD2 exomes

AF:

0.150

AC:

37697

AN:

251048

AF XY:

0.154

show subpopulations

Gnomad AFR exome

AF:

0.234

Gnomad AMR exome

AF:

0.0906

Gnomad ASJ exome

AF:

0.227

Gnomad EAS exome

AF:

0.0353

Gnomad FIN exome

AF:

0.114

Gnomad NFE exome

AF:

0.171

Gnomad OTH exome

AF:

0.166

GnomAD4 exome

AF:

0.163

AC:

238709

AN:

1461558

Hom.:

20604

Cov.:

AF XY:

0.163

AC XY:

118617

AN XY:

727064

show subpopulations

African (AFR)

AF:

0.235

AC:

7863

AN:

33478

American (AMR)

AF:

0.0931

AC:

4164

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.233

AC:

6080

AN:

26132

East Asian (EAS)

AF:

0.0217

AC:

860

AN:

39700

South Asian (SAS)

AF:

0.164

AC:

14108

AN:

86250

European-Finnish (FIN)

AF:

0.113

AC:

6057

AN:

53384

Middle Eastern (MID)

AF:

0.204

AC:

1178

AN:

5768

European-Non Finnish (NFE)

AF:

0.170

AC:

188583

AN:

1111752

Other (OTH)

AF:

0.163

AC:

9816

AN:

60370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

10304

20609

30913

41218

51522

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6656

13312

19968

26624

33280

<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:

0.173

AC:

26314

AN:

152088

Hom.:

2446

Cov.:

AF XY:

0.168

AC XY:

12521

AN XY:

74350

show subpopulations

African (AFR)

AF:

0.230

AC:

9520

AN:

41436

American (AMR)

AF:

0.130

AC:

1986

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.231

AC:

801

AN:

3468

East Asian (EAS)

AF:

0.0305

AC:

158

AN:

5182

South Asian (SAS)

AF:

0.153

AC:

736

AN:

4820

European-Finnish (FIN)

AF:

0.111

AC:

1181

AN:

10604

Middle Eastern (MID)

AF:

0.207

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.167

AC:

11344

AN:

67978

Other (OTH)

AF:

0.177

AC:

375

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

1093

2186

3279

4372

5465

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

274

548

822

1096

1370

<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:

0.178

Hom.:

1638

Bravo

AF:

0.178

Asia WGS

AF:

0.0790

AC:

274

AN:

3478

EpiCase

AF:

0.168

EpiControl

AF:

0.176

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

Nov 18, 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

-0.88

CADD

Benign

0.55

(source)

DANN

Benign

0.54

PhyloP100

-2.2

Mutation Taster

=86/14

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