Variant 17-78539866-T-C 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.2547A>G(p.Leu849=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.76 in 1,596,024 control chromosomes in the GnomAD database, including 461,199 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.77 ( 44625 hom., cov: 30)

Exomes 𝑓: 0.76 ( 416574 hom. )

Consequence

DNAH17
NM_173628.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.13

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=-0.9).

BP6

Variant 17-78539866-T-C is Benign according to our data. Variant chr17-78539866-T-C is described in ClinVar as [Benign]. Clinvar id is 402699.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.13 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.777 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.2547A>G	p.Leu849=	synonymous_variant	18/81	ENST00000389840.7	NP_775899.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAH17	ENST00000389840.7 linkuse as main transcript	c.2547A>G	p.Leu849=	synonymous_variant	18/81	5	NM_173628.4	ENSP00000374490	P1	Q9UFH2-1

Frequencies

GnomAD3 genomes

AF:

0.766

AC:

116282

AN:

151868

Hom.:

44580

Cov.:

show subpopulations

Gnomad AFR

AF:

0.784

Gnomad AMI

AF:

0.851

Gnomad AMR

AF:

0.728

Gnomad ASJ

AF:

0.754

Gnomad EAS

AF:

0.765

Gnomad SAS

AF:

0.732

Gnomad FIN

AF:

0.759

Gnomad MID

AF:

0.728

Gnomad NFE

AF:

0.766

Gnomad OTH

AF:

0.776

GnomAD3 exomes

AF:

0.754

AC:

175501

AN:

232736

Hom.:

66066

AF XY:

0.754

AC XY:

95813

AN XY:

127042

show subpopulations

Gnomad AFR exome

AF:

0.786

Gnomad AMR exome

AF:

0.710

Gnomad ASJ exome

AF:

0.759

Gnomad EAS exome

AF:

0.752

Gnomad SAS exome

AF:

0.736

Gnomad FIN exome

AF:

0.770

Gnomad NFE exome

AF:

0.763

Gnomad OTH exome

AF:

0.759

GnomAD4 exome

AF:

0.759

AC:

1096377

AN:

1444038

Hom.:

416574

Cov.:

AF XY:

0.758

AC XY:

544319

AN XY:

717712

show subpopulations

Gnomad4 AFR exome

AF:

0.789

Gnomad4 AMR exome

AF:

0.709

Gnomad4 ASJ exome

AF:

0.755

Gnomad4 EAS exome

AF:

0.787

Gnomad4 SAS exome

AF:

0.730

Gnomad4 FIN exome

AF:

0.775

Gnomad4 NFE exome

AF:

0.761

Gnomad4 OTH exome

AF:

0.761

GnomAD4 genome

AF:

0.766

AC:

116377

AN:

151986

Hom.:

44625

Cov.:

AF XY:

0.766

AC XY:

56930

AN XY:

74294

show subpopulations

Gnomad4 AFR

AF:

0.784

Gnomad4 AMR

AF:

0.728

Gnomad4 ASJ

AF:

0.754

Gnomad4 EAS

AF:

0.766

Gnomad4 SAS

AF:

0.733

Gnomad4 FIN

AF:

0.759

Gnomad4 NFE

AF:

0.766

Gnomad4 OTH

AF:

0.769

Alfa

AF:

0.759

Hom.:

21504

Bravo

AF:

0.763

Asia WGS

AF:

0.767

AC:

2666

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -

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

-0.90

CADD

Benign

0.65

DANN

Benign

0.36

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