dbSNP rs61746438: DNAH17:p.Asp2835Asp (chr17-78475284-G-A) – ACMG Classification: Benign (-18 pts)

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_173628.4(DNAH17):c.8505C>T(p.Asp2835Asp) variant causes a synonymous change. The variant allele was found at a frequency of 0.123 in 1,613,812 control chromosomes in the GnomAD database, including 13,092 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 1129 hom., cov: 32)

Exomes 𝑓: 0.12 ( 11963 hom. )

Consequence

DNAH17
NM_173628.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 4.10

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 -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.45).

BP6

Variant 17-78475284-G-A is Benign according to our data. Variant chr17-78475284-G-A is described in ClinVar as [Benign]. Clinvar id is 402678.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.18 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH17	NM_173628.4 link	c.8505C>T	p.Asp2835Asp	synonymous_variant	Exon 54 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.8505C>T	p.Asp2835Asp	synonymous_variant	Exon 54 of 81	5	NM_173628.4	ENSP00000374490.6		Q9UFH2-1
DNAH17	ENST00000586052.5 link	n.1887C>T		non_coding_transcript_exon_variant	Exon 10 of 35	5

Frequencies

GnomAD3 genomes

AF:

0.116

AC:

17638

AN:

152132

Hom.:

1123

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0867

Gnomad AMI

AF:

0.138

Gnomad AMR

AF:

0.0993

Gnomad ASJ

AF:

0.115

Gnomad EAS

AF:

0.190

Gnomad SAS

AF:

0.180

Gnomad FIN

AF:

0.161

Gnomad MID

AF:

0.114

Gnomad NFE

AF:

0.120

Gnomad OTH

AF:

0.119

GnomAD3 exomes

AF:

0.130

AC:

32432

AN:

248784

Hom.:

2376

AF XY:

0.136

AC XY:

18321

AN XY:

135024

show subpopulations

Gnomad AFR exome

AF:

0.0835

Gnomad AMR exome

AF:

0.0749

Gnomad ASJ exome

AF:

0.106

Gnomad EAS exome

AF:

0.195

Gnomad SAS exome

AF:

0.187

Gnomad FIN exome

AF:

0.159

Gnomad NFE exome

AF:

0.125

Gnomad OTH exome

AF:

0.135

GnomAD4 exome

AF:

0.124

AC:

181214

AN:

1461562

Hom.:

11963

Cov.:

AF XY:

0.126

AC XY:

91705

AN XY:

727062

show subpopulations

Gnomad4 AFR exome

AF:

0.0821

Gnomad4 AMR exome

AF:

0.0772

Gnomad4 ASJ exome

AF:

0.109

Gnomad4 EAS exome

AF:

0.157

Gnomad4 SAS exome

AF:

0.186

Gnomad4 FIN exome

AF:

0.159

Gnomad4 NFE exome

AF:

0.120

Gnomad4 OTH exome

AF:

0.129

GnomAD4 genome

AF:

0.116

AC:

17660

AN:

152250

Hom.:

1129

Cov.:

AF XY:

0.119

AC XY:

8844

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.0871

Gnomad4 AMR

AF:

0.0990

Gnomad4 ASJ

AF:

0.115

Gnomad4 EAS

AF:

0.190

Gnomad4 SAS

AF:

0.180

Gnomad4 FIN

AF:

0.161

Gnomad4 NFE

AF:

0.120

Gnomad4 OTH

AF:

0.122

Alfa

AF:

0.117

Hom.:

513

Bravo

AF:

0.108

Asia WGS

AF:

0.201

AC:

700

AN:

3478

EpiCase

AF:

0.124

EpiControl

AF:

0.128

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 04, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

BayesDel_noAF

Benign

-0.45

CADD

Benign

8.6

DANN

Benign

0.91

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