Variant 17-78486350-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_173628.4(DNAH17):c.6975T>C(p.Ile2325=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.656 in 1,613,636 control chromosomes in the GnomAD database, including 348,728 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.64 ( 31534 hom., cov: 31)

Exomes 𝑓: 0.66 ( 317194 hom. )

Consequence

DNAH17
NM_173628.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.167

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:

DNAH17-AS1 (HGNC:48594): (DNAH17 antisense RNA 1)

DNAH17-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BP6

Variant 17-78486350-A-G is Benign according to our data. Variant chr17-78486350-A-G is described in ClinVar as [Benign]. Clinvar id is 402681.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.167 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.731 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH17	NM_173628.4 linkuse as main transcript	c.6975T>C	p.Ile2325=	synonymous_variant	45/81	ENST00000389840.7
DNAH17-AS1	NR_102401.1 linkuse as main transcript	n.253+1188A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH17	ENST00000389840.7 linkuse as main transcript	c.6975T>C	p.Ile2325=	synonymous_variant	45/81	5	NM_173628.4	P1	Q9UFH2-1
DNAH17-AS1	ENST00000591373.2 linkuse as main transcript	n.253+1188A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.641

AC:

97332

AN:

151926

Hom.:

31501

Cov.:

show subpopulations

Gnomad AFR

AF:

0.575

Gnomad AMI

AF:

0.691

Gnomad AMR

AF:

0.742

Gnomad ASJ

AF:

0.702

Gnomad EAS

AF:

0.594

Gnomad SAS

AF:

0.721

Gnomad FIN

AF:

0.592

Gnomad MID

AF:

0.709

Gnomad NFE

AF:

0.658

Gnomad OTH

AF:

0.675

GnomAD3 exomes

AF:

0.675

AC:

168244

AN:

249176

Hom.:

57612

AF XY:

0.675

AC XY:

91185

AN XY:

135158

show subpopulations

Gnomad AFR exome

AF:

0.573

Gnomad AMR exome

AF:

0.810

Gnomad ASJ exome

AF:

0.699

Gnomad EAS exome

AF:

0.600

Gnomad SAS exome

AF:

0.731

Gnomad FIN exome

AF:

0.585

Gnomad NFE exome

AF:

0.660

Gnomad OTH exome

AF:

0.674

GnomAD4 exome

AF:

0.657

AC:

960642

AN:

1461592

Hom.:

317194

Cov.:

AF XY:

0.659

AC XY:

478961

AN XY:

727078

show subpopulations

Gnomad4 AFR exome

AF:

0.575

Gnomad4 AMR exome

AF:

0.801

Gnomad4 ASJ exome

AF:

0.693

Gnomad4 EAS exome

AF:

0.596

Gnomad4 SAS exome

AF:

0.727

Gnomad4 FIN exome

AF:

0.585

Gnomad4 NFE exome

AF:

0.653

Gnomad4 OTH exome

AF:

0.661

GnomAD4 genome

AF:

0.641

AC:

97412

AN:

152044

Hom.:

31534

Cov.:

AF XY:

0.641

AC XY:

47602

AN XY:

74308

show subpopulations

Gnomad4 AFR

AF:

0.576

Gnomad4 AMR

AF:

0.742

Gnomad4 ASJ

AF:

0.702

Gnomad4 EAS

AF:

0.595

Gnomad4 SAS

AF:

0.721

Gnomad4 FIN

AF:

0.592

Gnomad4 NFE

AF:

0.658

Gnomad4 OTH

AF:

0.671

Alfa

AF:

0.639

Hom.:

14025

Bravo

AF:

0.649

Asia WGS

AF:

0.706

AC:

2455

AN:

3478

EpiCase

AF:

0.669

EpiControl

AF:

0.666

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 07, 2019	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

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

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 17, 2019

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

-0.62

CADD

Benign

7.9

DANN

Benign

0.65

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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