Variant chr17-78561780-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.1770A>G(p.Lys590=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.955 in 1,613,294 control chromosomes in the GnomAD database, including 735,375 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.95 ( 68168 hom., cov: 32)

Exomes 𝑓: 0.96 ( 667207 hom. )

Consequence

DNAH17
NM_173628.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.538

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=-0.58).

BP6

Variant 17-78561780-T-C is Benign according to our data. Variant chr17-78561780-T-C is described in ClinVar as [Benign]. Clinvar id is 402701.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.538 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.955 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.1770A>G	p.Lys590=	synonymous_variant	12/81	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.1770A>G	p.Lys590=	synonymous_variant	12/81	5	NM_173628.4	ENSP00000374490	P1	Q9UFH2-1
DNAH17	ENST00000589793.1 linkuse as main transcript	n.982A>G		non_coding_transcript_exon_variant	8/13	2

Frequencies

GnomAD3 genomes

AF:

0.946

AC:

143946

AN:

152158

Hom.:

68131

Cov.:

show subpopulations

Gnomad AFR

AF:

0.937

Gnomad AMI

AF:

0.988

Gnomad AMR

AF:

0.953

Gnomad ASJ

AF:

0.938

Gnomad EAS

AF:

0.914

Gnomad SAS

AF:

0.931

Gnomad FIN

AF:

0.892

Gnomad MID

AF:

0.924

Gnomad NFE

AF:

0.962

Gnomad OTH

AF:

0.946

GnomAD3 exomes

AF:

0.946

AC:

235710

AN:

249200

Hom.:

111570

AF XY:

0.944

AC XY:

127410

AN XY:

134940

show subpopulations

Gnomad AFR exome

AF:

0.937

Gnomad AMR exome

AF:

0.968

Gnomad ASJ exome

AF:

0.936

Gnomad EAS exome

AF:

0.911

Gnomad SAS exome

AF:

0.928

Gnomad FIN exome

AF:

0.899

Gnomad NFE exome

AF:

0.961

Gnomad OTH exome

AF:

0.951

GnomAD4 exome

AF:

0.955

AC:

1395954

AN:

1461018

Hom.:

667207

Cov.:

AF XY:

0.954

AC XY:

693336

AN XY:

726732

show subpopulations

Gnomad4 AFR exome

AF:

0.936

Gnomad4 AMR exome

AF:

0.964

Gnomad4 ASJ exome

AF:

0.936

Gnomad4 EAS exome

AF:

0.912

Gnomad4 SAS exome

AF:

0.928

Gnomad4 FIN exome

AF:

0.904

Gnomad4 NFE exome

AF:

0.963

Gnomad4 OTH exome

AF:

0.954

GnomAD4 genome

AF:

0.946

AC:

144042

AN:

152276

Hom.:

68168

Cov.:

AF XY:

0.942

AC XY:

70164

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.937

Gnomad4 AMR

AF:

0.953

Gnomad4 ASJ

AF:

0.938

Gnomad4 EAS

AF:

0.914

Gnomad4 SAS

AF:

0.930

Gnomad4 FIN

AF:

0.892

Gnomad4 NFE

AF:

0.962

Gnomad4 OTH

AF:

0.942

Alfa

AF:

0.955

Hom.:

30049

Bravo

AF:

0.952

Asia WGS

AF:

0.926

AC:

3221

AN:

3478

EpiCase

AF:

0.961

EpiControl

AF:

0.959

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: MAF -

DNAH17-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 22, 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

-0.58

CADD

Benign

7.6

DANN

Benign

0.62

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