rs61742072

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_173628.4(DNAH17):c.11857C>T(p.His3953Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 1,611,708 control chromosomes in the GnomAD database, including 22,566 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H3953R) has been classified as Benign.

Frequency

Genomes: 𝑓 0.13 ( 1506 hom., cov: 29)

Exomes 𝑓: 0.17 ( 21060 hom. )

Consequence

DNAH17
NM_173628.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.63

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0015000999).

BP6

Variant 17-78437817-G-A is Benign according to our data. Variant chr17-78437817-G-A is described in ClinVar as [Benign]. Clinvar id is 402675.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.173 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH17	NM_173628.4 link	c.11857C>T	p.His3953Tyr	missense_variant	Exon 74 of 81	ENST00000389840.7	NP_775899.3	Q9UFH2-1
DNAH17	XM_011525416.3 link	c.11869C>T	p.His3957Tyr	missense_variant	Exon 74 of 81		XP_011523718.1
DNAH17	XM_024451013.2 link	c.11725C>T	p.His3909Tyr	missense_variant	Exon 73 of 80		XP_024306781.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DNAH17	ENST00000389840.7 link	c.11857C>T	p.His3953Tyr	missense_variant	Exon 74 of 81	5	NM_173628.4	ENSP00000374490.6	Q9UFH2-1
DNAH17	ENST00000586052.5 link	n.4993C>T		non_coding_transcript_exon_variant	Exon 28 of 35	5
DNAH17	ENST00000590227.5 link	n.1531C>T		non_coding_transcript_exon_variant	Exon 6 of 13	2
DNAH17	ENST00000591369.5 link	n.3457C>T		non_coding_transcript_exon_variant	Exon 21 of 28	5		ENSP00000466150.1	K7ELN3

Frequencies

GnomAD3 genomes

AF:

0.128

AC:

19476

AN:

152112

Hom.:

1505

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0523

Gnomad AMI

AF:

0.173

Gnomad AMR

AF:

0.115

Gnomad ASJ

AF:

0.199

Gnomad EAS

AF:

0.0943

Gnomad SAS

AF:

0.150

Gnomad FIN

AF:

0.112

Gnomad MID

AF:

0.190

Gnomad NFE

AF:

0.175

Gnomad OTH

AF:

0.147

GnomAD3 exomes

AF:

0.142

AC:

35251

AN:

248778

Hom.:

2874

AF XY:

0.149

AC XY:

20134

AN XY:

135106

show subpopulations

Gnomad AFR exome

AF:

0.0427

Gnomad AMR exome

AF:

0.0837

Gnomad ASJ exome

AF:

0.197

Gnomad EAS exome

AF:

0.0925

Gnomad SAS exome

AF:

0.152

Gnomad FIN exome

AF:

0.115

Gnomad NFE exome

AF:

0.178

Gnomad OTH exome

AF:

0.165

GnomAD4 exome

AF:

0.165

AC:

240842

AN:

1459478

Hom.:

21060

Cov.:

AF XY:

0.165

AC XY:

119862

AN XY:

725962

show subpopulations

Gnomad4 AFR exome

AF:

0.0447

Gnomad4 AMR exome

AF:

0.0860

Gnomad4 ASJ exome

AF:

0.203

Gnomad4 EAS exome

AF:

0.0773

Gnomad4 SAS exome

AF:

0.154

Gnomad4 FIN exome

AF:

0.114

Gnomad4 NFE exome

AF:

0.178

Gnomad4 OTH exome

AF:

0.156

GnomAD4 genome

AF:

0.128

AC:

19476

AN:

152230

Hom.:

1506

Cov.:

AF XY:

0.125

AC XY:

9282

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.0524

Gnomad4 AMR

AF:

0.115

Gnomad4 ASJ

AF:

0.199

Gnomad4 EAS

AF:

0.0939

Gnomad4 SAS

AF:

0.150

Gnomad4 FIN

AF:

0.112

Gnomad4 NFE

AF:

0.175

Gnomad4 OTH

AF:

0.146

Alfa

AF:

0.165

Hom.:

2283

Bravo

AF:

0.125

TwinsUK

AF:

0.172

AC:

639

ALSPAC

AF:

0.179

AC:

691

ESP6500AA

AF:

0.0461

AC:

203

ESP6500EA

AF:

0.167

AC:

1438

ExAC

AF:

0.146

AC:

17709

Asia WGS

AF:

0.103

AC:

360

AN:

3478

EpiCase

AF:

0.177

EpiControl

AF:

0.186

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Apr 19, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 30389748) -

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

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.24

.;T

Eigen

Benign

-0.26

Eigen_PC

Benign

-0.13

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.66

T;T

MetaRNN

Benign

0.0015

T;T

MetaSVM

Benign

-0.97

PrimateAI

Benign

0.35

PROVEAN

Pathogenic

-5.4

.;D

REVEL

Benign

0.084

Sift

Pathogenic

0.0

.;D

Vest4

0.14

ClinPred

0.059

GERP RS

3.0

Varity_R

0.71

gMVP

0.38

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over