Variant chr17-78529483-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.3496T>C(p.Leu1166Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.609 in 1,613,440 control chromosomes in the GnomAD database, including 300,753 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.61 ( 28713 hom., cov: 30)

Exomes 𝑓: 0.61 ( 272040 hom. )

Consequence

DNAH17
NM_173628.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.00900

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 17-78529483-A-G is Benign according to our data. Variant chr17-78529483-A-G is described in ClinVar as [Benign]. Clinvar id is 402694.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.009 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.63 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH17	NM_173628.4 linkuse as main transcript	c.3496T>C	p.Leu1166Leu	synonymous_variant	22/81	ENST00000389840.7	NP_775899.3	Q9UFH2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAH17	ENST00000389840.7 linkuse as main transcript	c.3496T>C	p.Leu1166Leu	synonymous_variant	22/81	5	NM_173628.4	ENSP00000374490.6		Q9UFH2-1

Frequencies

GnomAD3 genomes

AF:

0.613

AC:

92970

AN:

151750

Hom.:

28689

Cov.:

show subpopulations

Gnomad AFR

AF:

0.636

Gnomad AMI

AF:

0.676

Gnomad AMR

AF:

0.590

Gnomad ASJ

AF:

0.575

Gnomad EAS

AF:

0.602

Gnomad SAS

AF:

0.499

Gnomad FIN

AF:

0.534

Gnomad MID

AF:

0.642

Gnomad NFE

AF:

0.624

Gnomad OTH

AF:

0.647

GnomAD3 exomes

AF:

0.589

AC:

146709

AN:

249090

Hom.:

43740

AF XY:

0.588

AC XY:

79459

AN XY:

135168

show subpopulations

Gnomad AFR exome

AF:

0.634

Gnomad AMR exome

AF:

0.551

Gnomad ASJ exome

AF:

0.593

Gnomad EAS exome

AF:

0.614

Gnomad SAS exome

AF:

0.495

Gnomad FIN exome

AF:

0.540

Gnomad NFE exome

AF:

0.624

Gnomad OTH exome

AF:

0.603

GnomAD4 exome

AF:

0.609

AC:

889810

AN:

1461572

Hom.:

272040

Cov.:

AF XY:

0.606

AC XY:

440456

AN XY:

727066

show subpopulations

Gnomad4 AFR exome

AF:

0.635

Gnomad4 AMR exome

AF:

0.557

Gnomad4 ASJ exome

AF:

0.589

Gnomad4 EAS exome

AF:

0.588

Gnomad4 SAS exome

AF:

0.504

Gnomad4 FIN exome

AF:

0.541

Gnomad4 NFE exome

AF:

0.622

Gnomad4 OTH exome

AF:

0.612

GnomAD4 genome

AF:

0.613

AC:

93041

AN:

151868

Hom.:

28713

Cov.:

AF XY:

0.606

AC XY:

44985

AN XY:

74238

show subpopulations

Gnomad4 AFR

AF:

0.636

Gnomad4 AMR

AF:

0.591

Gnomad4 ASJ

AF:

0.575

Gnomad4 EAS

AF:

0.602

Gnomad4 SAS

AF:

0.498

Gnomad4 FIN

AF:

0.534

Gnomad4 NFE

AF:

0.624

Gnomad4 OTH

AF:

0.642

Alfa

AF:

0.628

Hom.:

58941

Bravo

AF:

0.622

Asia WGS

AF:

0.540

AC:

1878

AN:

3478

EpiCase

AF:

0.636

EpiControl

AF:

0.643

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

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). -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.090

DANN

Benign

0.53

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