Genetic Variant NM_173628.4:c.4500G>A (chr17-78507542-C-T) – ACMG Classification: Benign (-19 pts)

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_173628.4(DNAH17):c.4500G>A(p.Glu1500Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.253 in 1,613,666 control chromosomes in the GnomAD database, including 55,734 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.25 ( 5201 hom., cov: 33)

Exomes 𝑓: 0.25 ( 50533 hom. )

Consequence

DNAH17
NM_173628.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.710

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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.42).

BP6

Variant 17-78507542-C-T is Benign according to our data. Variant chr17-78507542-C-T is described in ClinVar as [Benign]. Clinvar id is 402691.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.71 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.451 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH17	NM_173628.4 link	c.4500G>A	p.Glu1500Glu	synonymous_variant	Exon 28 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.4500G>A	p.Glu1500Glu	synonymous_variant	Exon 28 of 81	5	NM_173628.4	ENSP00000374490.6		Q9UFH2-1
DNAH17	ENST00000587177.1 link	n.552G>A		non_coding_transcript_exon_variant	Exon 2 of 7	5

Frequencies

GnomAD3 genomes

AF:

0.249

AC:

37842

AN:

152044

Hom.:

5192

Cov.:

show subpopulations

Gnomad AFR

AF:

0.187

Gnomad AMI

AF:

0.283

Gnomad AMR

AF:

0.377

Gnomad ASJ

AF:

0.192

Gnomad EAS

AF:

0.467

Gnomad SAS

AF:

0.377

Gnomad FIN

AF:

0.310

Gnomad MID

AF:

0.177

Gnomad NFE

AF:

0.226

Gnomad OTH

AF:

0.229

GnomAD3 exomes

AF:

0.300

AC:

74590

AN:

248720

Hom.:

12891

AF XY:

0.295

AC XY:

39794

AN XY:

134954

show subpopulations

Gnomad AFR exome

AF:

0.191

Gnomad AMR exome

AF:

0.473

Gnomad ASJ exome

AF:

0.184

Gnomad EAS exome

AF:

0.470

Gnomad SAS exome

AF:

0.375

Gnomad FIN exome

AF:

0.302

Gnomad NFE exome

AF:

0.227

Gnomad OTH exome

AF:

0.260

GnomAD4 exome

AF:

0.253

AC:

369876

AN:

1461504

Hom.:

50533

Cov.:

AF XY:

0.255

AC XY:

185674

AN XY:

727010

show subpopulations

Gnomad4 AFR exome

AF:

0.188

Gnomad4 AMR exome

AF:

0.459

Gnomad4 ASJ exome

AF:

0.187

Gnomad4 EAS exome

AF:

0.465

Gnomad4 SAS exome

AF:

0.370

Gnomad4 FIN exome

AF:

0.301

Gnomad4 NFE exome

AF:

0.230

Gnomad4 OTH exome

AF:

0.249

GnomAD4 genome

AF:

0.249

AC:

37880

AN:

152162

Hom.:

5201

Cov.:

AF XY:

0.259

AC XY:

19242

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.187

Gnomad4 AMR

AF:

0.377

Gnomad4 ASJ

AF:

0.192

Gnomad4 EAS

AF:

0.467

Gnomad4 SAS

AF:

0.379

Gnomad4 FIN

AF:

0.310

Gnomad4 NFE

AF:

0.226

Gnomad4 OTH

AF:

0.235

Alfa

AF:

0.232

Hom.:

5492

Bravo

AF:

0.251

Asia WGS

AF:

0.382

AC:

1325

AN:

3478

EpiCase

AF:

0.214

EpiControl

AF:

0.221

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

BayesDel_noAF

Benign

-0.42

CADD

Benign

8.5

DANN

Benign

0.68

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