17-78502610-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_173628.4(DNAH17):c.5171G>A(p.Arg1724Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.838 in 1,612,524 control chromosomes in the GnomAD database, including 568,007 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.87 ( 58178 hom., cov: 32)

Exomes 𝑓: 0.83 ( 509829 hom. )

Consequence

DNAH17
NM_173628.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.91

Publications

23 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 links:

DNAH17-AS1 (HGNC:48594): (DNAH17 antisense RNA 1)

DNAH17-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=6.9313097E-7).

BP6

Variant 17-78502610-C-T is Benign according to our data. Variant chr17-78502610-C-T is described in ClinVar as Benign. ClinVar VariationId is 402687.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.96 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH17	NM_173628.4 link	c.5171G>A	p.Arg1724Lys	missense_variant	Exon 33 of 81	ENST00000389840.7	NP_775899.3	Q9UFH2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DNAH17	ENST00000389840.7 link	c.5171G>A	p.Arg1724Lys	missense_variant	Exon 33 of 81	5	NM_173628.4	ENSP00000374490.6	Q9UFH2-1
DNAH17-AS1	ENST00000598378.2 link	n.4151C>T		non_coding_transcript_exon_variant	Exon 2 of 2	2
DNAH17	ENST00000587177.1 link	n.1135-73G>A		intron_variant	Intron 6 of 6	5

Frequencies

GnomAD3 genomes

AF:

0.871

AC:

132484

AN:

152158

Hom.:

58116

Cov.:

show subpopulations

Gnomad AFR

AF:

0.967

Gnomad AMI

AF:

0.821

Gnomad AMR

AF:

0.879

Gnomad ASJ

AF:

0.876

Gnomad EAS

AF:

0.978

Gnomad SAS

AF:

0.932

Gnomad FIN

AF:

0.810

Gnomad MID

AF:

0.870

Gnomad NFE

AF:

0.807

Gnomad OTH

AF:

0.877

GnomAD2 exomes

AF:

0.865

AC:

213738

AN:

247090

AF XY:

0.862

show subpopulations

Gnomad AFR exome

AF:

0.972

Gnomad AMR exome

AF:

0.919

Gnomad ASJ exome

AF:

0.870

Gnomad EAS exome

AF:

0.977

Gnomad FIN exome

AF:

0.810

Gnomad NFE exome

AF:

0.810

Gnomad OTH exome

AF:

0.848

GnomAD4 exome

AF:

0.834

AC:

1218005

AN:

1460248

Hom.:

509829

Cov.:

AF XY:

0.835

AC XY:

606759

AN XY:

726394

show subpopulations

African (AFR)

AF:

0.975

AC:

32615

AN:

33446

American (AMR)

AF:

0.915

AC:

40715

AN:

44476

Ashkenazi Jewish (ASJ)

AF:

0.870

AC:

22716

AN:

26122

East Asian (EAS)

AF:

0.988

AC:

39199

AN:

39686

South Asian (SAS)

AF:

0.925

AC:

79698

AN:

86140

European-Finnish (FIN)

AF:

0.811

AC:

42953

AN:

52956

Middle Eastern (MID)

AF:

0.862

AC:

4972

AN:

5766

European-Non Finnish (NFE)

AF:

0.813

AC:

903644

AN:

1111320

Other (OTH)

AF:

0.853

AC:

51493

AN:

60336

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

9750

19500

29250

39000

48750

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20994

41988

62982

83976

104970

<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:

0.871

AC:

132605

AN:

152276

Hom.:

58178

Cov.:

AF XY:

0.873

AC XY:

65030

AN XY:

74460

show subpopulations

African (AFR)

AF:

0.967

AC:

40217

AN:

41568

American (AMR)

AF:

0.880

AC:

13450

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.876

AC:

3041

AN:

3470

East Asian (EAS)

AF:

0.978

AC:

5065

AN:

5180

South Asian (SAS)

AF:

0.932

AC:

4496

AN:

4826

European-Finnish (FIN)

AF:

0.810

AC:

8596

AN:

10606

Middle Eastern (MID)

AF:

0.864

AC:

254

AN:

294

European-Non Finnish (NFE)

AF:

0.807

AC:

54879

AN:

68014

Other (OTH)

AF:

0.879

AC:

1858

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

860

1720

2580

3440

4300

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

896

1792

2688

3584

4480

<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:

0.842

Hom.:

101997

Bravo

AF:

0.881

TwinsUK

AF:

0.817

AC:

3029

ALSPAC

AF:

0.814

AC:

3139

ESP6500AA

AF:

0.971

AC:

3895

ESP6500EA

AF:

0.812

AC:

6854

ExAC

AF:

0.864

AC:

104442

Asia WGS

AF:

0.965

AC:

3357

AN:

3478

EpiCase

AF:

0.809

EpiControl

AF:

0.814

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

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). -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.71

CADD

Benign

(source)

DANN

Benign

0.46

Eigen

Benign

-0.47

Eigen_PC

Benign

-0.44

FATHMM_MKL

Benign

0.027

LIST_S2

Benign

0.58

T;T

MetaRNN

Benign

6.9e-7

T;T

MetaSVM

Benign

-0.93

PhyloP100

1.9

PrimateAI

Uncertain

0.49

REVEL

Benign

0.054

Vest4

0.024

ClinPred

0.010

GERP RS

3.3

Varity_R

0.060

gMVP

0.22

Mutation Taster

=99/1

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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