17-78532708-A-G

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.2888T>C(p.Ile963Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.514 in 1,590,510 control chromosomes in the GnomAD database, including 211,095 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.51 ( 19651 hom., cov: 31)

Exomes 𝑓: 0.51 ( 191444 hom. )

Consequence

DNAH17
NM_173628.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.338

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:

RN7SL454P (HGNC:46470): (RNA, 7SL, cytoplasmic 454, pseudogene)

RN7SL454P 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=1.5595555E-4).

BP6

Variant 17-78532708-A-G is Benign according to our data. Variant chr17-78532708-A-G is described in ClinVar as Benign. ClinVar VariationId is 402697.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.532 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH17	NM_173628.4 link	c.2888T>C	p.Ile963Thr	missense_variant	Exon 20 of 81	ENST00000389840.7	NP_775899.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH17	ENST00000389840.7 link	c.2888T>C	p.Ile963Thr	missense_variant	Exon 20 of 81	5	NM_173628.4	ENSP00000374490.6
RN7SL454P	ENST00000492744.3 link	n.*105T>C		downstream_gene_variant		6

Frequencies

GnomAD3 genomes

AF:

0.506

AC:

76780

AN:

151748

Hom.:

19642

Cov.:

show subpopulations

Gnomad AFR

AF:

0.490

Gnomad AMI

AF:

0.753

Gnomad AMR

AF:

0.435

Gnomad ASJ

AF:

0.511

Gnomad EAS

AF:

0.429

Gnomad SAS

AF:

0.421

Gnomad FIN

AF:

0.524

Gnomad MID

AF:

0.525

Gnomad NFE

AF:

0.536

Gnomad OTH

AF:

0.520

GnomAD2 exomes

AF:

0.481

AC:

104088

AN:

216402

AF XY:

0.485

show subpopulations

Gnomad AFR exome

AF:

0.478

Gnomad AMR exome

AF:

0.376

Gnomad ASJ exome

AF:

0.519

Gnomad EAS exome

AF:

0.425

Gnomad FIN exome

AF:

0.516

Gnomad NFE exome

AF:

0.529

Gnomad OTH exome

AF:

0.510

GnomAD4 exome

AF:

0.514

AC:

740145

AN:

1438644

Hom.:

191444

Cov.:

AF XY:

0.513

AC XY:

365806

AN XY:

713286

show subpopulations

African (AFR)

AF:

0.483

AC:

15971

AN:

33094

American (AMR)

AF:

0.383

AC:

16001

AN:

41784

Ashkenazi Jewish (ASJ)

AF:

0.522

AC:

13320

AN:

25518

East Asian (EAS)

AF:

0.439

AC:

17171

AN:

39102

South Asian (SAS)

AF:

0.434

AC:

35977

AN:

82940

European-Finnish (FIN)

AF:

0.521

AC:

27078

AN:

51944

Middle Eastern (MID)

AF:

0.542

AC:

3051

AN:

5626

European-Non Finnish (NFE)

AF:

0.529

AC:

581011

AN:

1099062

Other (OTH)

AF:

0.513

AC:

30565

AN:

59574

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

17845

35691

53536

71382

89227

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16594

33188

49782

66376

82970

<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:

0.506

AC:

76821

AN:

151866

Hom.:

19651

Cov.:

AF XY:

0.502

AC XY:

37239

AN XY:

74210

show subpopulations

African (AFR)

AF:

0.490

AC:

20267

AN:

41374

American (AMR)

AF:

0.435

AC:

6635

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.511

AC:

1773

AN:

3468

East Asian (EAS)

AF:

0.429

AC:

2218

AN:

5168

South Asian (SAS)

AF:

0.422

AC:

2027

AN:

4808

European-Finnish (FIN)

AF:

0.524

AC:

5531

AN:

10552

Middle Eastern (MID)

AF:

0.531

AC:

155

AN:

292

European-Non Finnish (NFE)

AF:

0.536

AC:

36444

AN:

67934

Other (OTH)

AF:

0.517

AC:

1086

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1944

3888

5833

7777

9721

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

684

1368

2052

2736

3420

<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:

0.516

Hom.:

37421

Bravo

AF:

0.499

TwinsUK

AF:

0.521

AC:

1932

ALSPAC

AF:

0.529

AC:

2040

ESP6500AA

AF:

0.499

AC:

1965

ESP6500EA

AF:

0.531

AC:

4411

ExAC

AF:

0.463

AC:

55419

Asia WGS

AF:

0.429

AC:

1491

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

0.074

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.55

CADD

Benign

9.9

(source)

DANN

Benign

0.60

DEOGEN2

Benign

0.0

.;T

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.34

FATHMM_MKL

Benign

0.033

LIST_S2

Benign

0.59

T;T

MetaRNN

Benign

0.00016

T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.0

.;L

PhyloP100

0.34

PrimateAI

Benign

0.38

PROVEAN

Benign

0.0

.;N

REVEL

Benign

0.0

Sift

Pathogenic

0.0

.;T

Sift4G

Pathogenic

0.0

.;.

Vest4

0.039

ClinPred

0.0076

GERP RS

3.0

Varity_R

0.062

gMVP

0.25

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over