chr17-78437816-T-C

Variant names:

Variant summary

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

The NM_173628.4(DNAH17):c.11858A>G(p.His3953Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.991 in 1,612,240 control chromosomes in the GnomAD database, including 792,214 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.95 ( 69689 hom., cov: 33)

Exomes 𝑓: 0.99 ( 722525 hom. )

Consequence

DNAH17
NM_173628.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.135

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=6.583821E-7).

BP6

Variant 17-78437816-T-C is Benign according to our data. Variant chr17-78437816-T-C is described in ClinVar as [Benign]. Clinvar id is 402674.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH17	NM_173628.4 link	c.11858A>G	p.His3953Arg	missense_variant	Exon 74 of 81	ENST00000389840.7	NP_775899.3	Q9UFH2-1
DNAH17	XM_011525416.3 link	c.11870A>G	p.His3957Arg	missense_variant	Exon 74 of 81		XP_011523718.1
DNAH17	XM_024451013.2 link	c.11726A>G	p.His3909Arg	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.11858A>G	p.His3953Arg	missense_variant	Exon 74 of 81	5	NM_173628.4	ENSP00000374490.6	Q9UFH2-1
DNAH17	ENST00000586052.5 link	n.4994A>G		non_coding_transcript_exon_variant	Exon 28 of 35	5
DNAH17	ENST00000590227.5 link	n.1532A>G		non_coding_transcript_exon_variant	Exon 6 of 13	2
DNAH17	ENST00000591369.5 link	n.3458A>G		non_coding_transcript_exon_variant	Exon 21 of 28	5		ENSP00000466150.1	K7ELN3

Frequencies

GnomAD3 genomes

AF:

0.954

AC:

145230

AN:

152158

Hom.:

69664

Cov.:

show subpopulations

Gnomad AFR

AF:

0.847

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.977

Gnomad ASJ

AF:

0.970

Gnomad EAS

AF:

0.999

Gnomad SAS

AF:

0.999

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

0.984

Gnomad NFE

AF:

0.999

Gnomad OTH

AF:

0.956

GnomAD3 exomes

AF:

0.987

AC:

245818

AN:

249138

Hom.:

121459

AF XY:

0.990

AC XY:

133884

AN XY:

135268

show subpopulations

Gnomad AFR exome

AF:

0.842

Gnomad AMR exome

AF:

0.989

Gnomad ASJ exome

AF:

0.976

Gnomad EAS exome

AF:

1.00

Gnomad SAS exome

AF:

1.00

Gnomad FIN exome

AF:

1.00

Gnomad NFE exome

AF:

0.999

Gnomad OTH exome

AF:

0.990

GnomAD4 exome

AF:

0.995

AC:

1452017

AN:

1459964

Hom.:

722525

Cov.:

AF XY:

0.995

AC XY:

722794

AN XY:

726246

show subpopulations

Gnomad4 AFR exome

AF:

0.839

Gnomad4 AMR exome

AF:

0.988

Gnomad4 ASJ exome

AF:

0.974

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

1.00

Gnomad4 FIN exome

AF:

1.00

Gnomad4 NFE exome

AF:

1.00

Gnomad4 OTH exome

AF:

0.986

GnomAD4 genome

AF:

0.954

AC:

145307

AN:

152276

Hom.:

69689

Cov.:

AF XY:

0.956

AC XY:

71138

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.847

Gnomad4 AMR

AF:

0.977

Gnomad4 ASJ

AF:

0.970

Gnomad4 EAS

AF:

0.999

Gnomad4 SAS

AF:

0.999

Gnomad4 FIN

AF:

1.00

Gnomad4 NFE

AF:

0.999

Gnomad4 OTH

AF:

0.955

Alfa

AF:

0.988

Hom.:

86132

Bravo

AF:

0.947

TwinsUK

AF:

0.999

AC:

3704

ALSPAC

AF:

1.00

AC:

3853

ESP6500AA

AF:

0.848

AC:

3733

ESP6500EA

AF:

0.998

AC:

8580

ExAC

AF:

0.985

AC:

119093

Asia WGS

AF:

0.980

AC:

3407

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 28, 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

0.056

BayesDel_addAF

Benign

-0.80

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.86

DANN

Benign

0.28

DEOGEN2

Benign

0.17

.;T

Eigen

Benign

-0.80

Eigen_PC

Benign

-0.68

FATHMM_MKL

Benign

0.047

LIST_S2

Benign

0.060

T;T

MetaRNN

Benign

6.6e-7

T;T

MetaSVM

Benign

-0.93

PrimateAI

Benign

0.34

PROVEAN

Pathogenic

-7.1

.;D

REVEL

Benign

0.12

Sift

Uncertain

0.0010

.;D

Vest4

0.027

ClinPred

0.041

GERP RS

4.1

Varity_R

0.44

gMVP

0.34

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