17-78453423-G-C

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.10449C>G(p.Thr3483Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.543 in 1,613,054 control chromosomes in the GnomAD database, including 241,327 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.49 ( 19086 hom., cov: 34)

Exomes 𝑓: 0.55 ( 222241 hom. )

Consequence

DNAH17
NM_173628.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.319

Publications

16 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=-0.51).

BP6

Variant 17-78453423-G-C is Benign according to our data. Variant chr17-78453423-G-C is described in ClinVar as Benign. ClinVar VariationId is 402676.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.319 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.616 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173628.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH17	NM_173628.4	MANE Select	c.10449C>G	p.Thr3483Thr	synonymous	Exon 65 of 81	NP_775899.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
DNAH17	ENST00000389840.7	TSL:5 MANE Select	c.10449C>G	p.Thr3483Thr	synonymous	Exon 65 of 81	ENSP00000374490.6
DNAH17	ENST00000586052.5	TSL:5	n.3734C>G		non_coding_transcript_exon	Exon 20 of 35
DNAH17	ENST00000591369.5	TSL:5	n.2049C>G		non_coding_transcript_exon	Exon 12 of 28	ENSP00000466150.1

Frequencies

GnomAD3 genomes

AF:

0.490

AC:

74539

AN:

152064

Hom.:

19072

Cov.:

show subpopulations

Gnomad AFR

AF:

0.344

Gnomad AMI

AF:

0.451

Gnomad AMR

AF:

0.507

Gnomad ASJ

AF:

0.602

Gnomad EAS

AF:

0.635

Gnomad SAS

AF:

0.412

Gnomad FIN

AF:

0.538

Gnomad MID

AF:

0.633

Gnomad NFE

AF:

0.556

Gnomad OTH

AF:

0.527

GnomAD2 exomes

AF:

0.521

AC:

130131

AN:

249610

AF XY:

0.524

show subpopulations

Gnomad AFR exome

AF:

0.326

Gnomad AMR exome

AF:

0.484

Gnomad ASJ exome

AF:

0.585

Gnomad EAS exome

AF:

0.641

Gnomad FIN exome

AF:

0.537

Gnomad NFE exome

AF:

0.559

Gnomad OTH exome

AF:

0.563

GnomAD4 exome

AF:

0.548

AC:

801073

AN:

1460872

Hom.:

222241

Cov.:

AF XY:

0.545

AC XY:

396122

AN XY:

726668

show subpopulations

African (AFR)

AF:

0.336

AC:

11236

AN:

33468

American (AMR)

AF:

0.486

AC:

21669

AN:

44580

Ashkenazi Jewish (ASJ)

AF:

0.588

AC:

15355

AN:

26118

East Asian (EAS)

AF:

0.605

AC:

23980

AN:

39662

South Asian (SAS)

AF:

0.417

AC:

35926

AN:

86162

European-Finnish (FIN)

AF:

0.542

AC:

28914

AN:

53348

Middle Eastern (MID)

AF:

0.644

AC:

3712

AN:

5766

European-Non Finnish (NFE)

AF:

0.564

AC:

626937

AN:

1111422

Other (OTH)

AF:

0.553

AC:

33344

AN:

60346

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

17929

35857

53786

71714

89643

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17542

35084

52626

70168

87710

<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:

0.490

AC:

74573

AN:

152182

Hom.:

19086

Cov.:

AF XY:

0.489

AC XY:

36414

AN XY:

74396

show subpopulations

African (AFR)

AF:

0.343

AC:

14258

AN:

41522

American (AMR)

AF:

0.507

AC:

7747

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.602

AC:

2090

AN:

3472

East Asian (EAS)

AF:

0.634

AC:

3288

AN:

5184

South Asian (SAS)

AF:

0.412

AC:

1986

AN:

4824

European-Finnish (FIN)

AF:

0.538

AC:

5703

AN:

10596

Middle Eastern (MID)

AF:

0.626

AC:

184

AN:

294

European-Non Finnish (NFE)

AF:

0.556

AC:

37783

AN:

67976

Other (OTH)

AF:

0.532

AC:

1123

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1936

3872

5808

7744

9680

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

668

1336

2004

2672

3340

<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:

0.544

Hom.:

7419

Bravo

AF:

0.485

Asia WGS

AF:

0.506

AC:

1761

AN:

3478

EpiCase

AF:

0.562

EpiControl

AF:

0.582

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 v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

4.4

(source)

DANN

Benign

0.62

PhyloP100

-0.32

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over