rs691652

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.5956A>G(p.Met1986Val) variant causes a missense change. The variant allele was found at a frequency of 0.838 in 1,610,590 control chromosomes in the GnomAD database, including 568,113 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.87 ( 58109 hom., cov: 34)

Exomes 𝑓: 0.83 ( 510004 hom. )

Consequence

DNAH17
NM_173628.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 5.96

Publications

21 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=7.9940725E-7).

BP6

Variant 17-78495045-T-C is Benign according to our data. Variant chr17-78495045-T-C is described in ClinVar as Benign. ClinVar VariationId is 402682.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.5956A>G	p.Met1986Val	missense_variant	Exon 39 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.5956A>G	p.Met1986Val	missense_variant	Exon 39 of 81	5	NM_173628.4	ENSP00000374490.6		Q9UFH2-1
DNAH17-AS1	ENST00000591373.2 link	n.769+848T>C		intron_variant	Intron 4 of 5	5

Frequencies

GnomAD3 genomes

AF:

0.871

AC:

132319

AN:

151944

Hom.:

58046

Cov.:

show subpopulations

Gnomad AFR

AF:

0.968

Gnomad AMI

AF:

0.820

Gnomad AMR

AF:

0.880

Gnomad ASJ

AF:

0.858

Gnomad EAS

AF:

0.978

Gnomad SAS

AF:

0.932

Gnomad FIN

AF:

0.808

Gnomad MID

AF:

0.864

Gnomad NFE

AF:

0.808

Gnomad OTH

AF:

0.877

GnomAD2 exomes

AF:

0.864

AC:

210604

AN:

243816

AF XY:

0.861

show subpopulations

Gnomad AFR exome

AF:

0.971

Gnomad AMR exome

AF:

0.916

Gnomad ASJ exome

AF:

0.851

Gnomad EAS exome

AF:

0.977

Gnomad FIN exome

AF:

0.809

Gnomad NFE exome

AF:

0.810

Gnomad OTH exome

AF:

0.846

GnomAD4 exome

AF:

0.835

AC:

1217715

AN:

1458528

Hom.:

510004

Cov.:

AF XY:

0.836

AC XY:

606370

AN XY:

725306

show subpopulations

African (AFR)

AF:

0.975

AC:

32606

AN:

33440

American (AMR)

AF:

0.913

AC:

40502

AN:

44340

Ashkenazi Jewish (ASJ)

AF:

0.851

AC:

22178

AN:

26048

East Asian (EAS)

AF:

0.988

AC:

39152

AN:

39636

South Asian (SAS)

AF:

0.926

AC:

79475

AN:

85796

European-Finnish (FIN)

AF:

0.811

AC:

42953

AN:

52950

Middle Eastern (MID)

AF:

0.861

AC:

4957

AN:

5760

European-Non Finnish (NFE)

AF:

0.815

AC:

904517

AN:

1110290

Other (OTH)

AF:

0.852

AC:

51375

AN:

60268

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

11395

22791

34186

45582

56977

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:

132442

AN:

152062

Hom.:

58109

Cov.:

AF XY:

0.873

AC XY:

64892

AN XY:

74298

show subpopulations

African (AFR)

AF:

0.968

AC:

40209

AN:

41544

American (AMR)

AF:

0.880

AC:

13459

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.858

AC:

2973

AN:

3466

East Asian (EAS)

AF:

0.978

AC:

5061

AN:

5176

South Asian (SAS)

AF:

0.932

AC:

4498

AN:

4824

European-Finnish (FIN)

AF:

0.808

AC:

8526

AN:

10546

Middle Eastern (MID)

AF:

0.857

AC:

252

AN:

294

European-Non Finnish (NFE)

AF:

0.808

AC:

54869

AN:

67906

Other (OTH)

AF:

0.879

AC:

1854

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

860

1720

2579

3439

4299

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

892

1784

2676

3568

4460

<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:

0.835

Hom.:

119361

Bravo

AF:

0.881

TwinsUK

AF:

0.819

AC:

3038

ALSPAC

AF:

0.816

AC:

3144

ESP6500AA

AF:

0.971

AC:

3968

ESP6500EA

AF:

0.814

AC:

6834

ExAC

AF:

0.857

AC:

103527

Asia WGS

AF:

0.965

AC:

3357

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 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 v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.041

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.63

CADD

Benign

(source)

DANN

Benign

0.52

Eigen

Benign

-0.29

Eigen_PC

Benign

-0.20

FATHMM_MKL

Benign

0.033

LIST_S2

Benign

0.60

T;T

MetaRNN

Benign

8.0e-7

T;T

MetaSVM

Benign

-0.93

PhyloP100

6.0

PrimateAI

Uncertain

0.78

REVEL

Benign

0.092

Vest4

0.090

ClinPred

0.014

GERP RS

3.8

Varity_R

0.10

gMVP

0.48

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

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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