Variant chr17-78495046-G-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.5955C>G(p.Leu1985=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.838 in 1,610,586 control chromosomes in the GnomAD database, including 567,584 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.87 ( 58070 hom., cov: 34)

Exomes 𝑓: 0.83 ( 509514 hom. )

Consequence

DNAH17
NM_173628.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.916

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=-0.55).

BP6

Variant 17-78495046-G-C is Benign according to our data. Variant chr17-78495046-G-C is described in ClinVar as [Benign]. Clinvar id is 402683.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.916 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.96 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.5955C>G	p.Leu1985=	synonymous_variant	39/81	ENST00000389840.7	NP_775899.3
DNAH17-AS1	NR_102401.1 linkuse as main transcript	n.769+849G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAH17	ENST00000389840.7 linkuse as main transcript	c.5955C>G	p.Leu1985=	synonymous_variant	39/81	5	NM_173628.4	ENSP00000374490	P1	Q9UFH2-1
DNAH17-AS1	ENST00000591373.2 linkuse as main transcript	n.769+849G>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.870

AC:

132271

AN:

151950

Hom.:

58007

Cov.:

show subpopulations

Gnomad AFR

AF:

0.968

Gnomad AMI

AF:

0.820

Gnomad AMR

AF:

0.880

Gnomad ASJ

AF:

0.856

Gnomad EAS

AF:

0.978

Gnomad SAS

AF:

0.933

Gnomad FIN

AF:

0.808

Gnomad MID

AF:

0.864

Gnomad NFE

AF:

0.807

Gnomad OTH

AF:

0.876

GnomAD3 exomes

AF:

0.863

AC:

210518

AN:

243820

Hom.:

91400

AF XY:

0.861

AC XY:

114050

AN XY:

132498

show subpopulations

Gnomad AFR exome

AF:

0.971

Gnomad AMR exome

AF:

0.916

Gnomad ASJ exome

AF:

0.849

Gnomad EAS exome

AF:

0.977

Gnomad SAS exome

AF:

0.928

Gnomad FIN exome

AF:

0.808

Gnomad NFE exome

AF:

0.810

Gnomad OTH exome

AF:

0.845

GnomAD4 exome

AF:

0.834

AC:

1217101

AN:

1458518

Hom.:

509514

Cov.:

AF XY:

0.836

AC XY:

606050

AN XY:

725304

show subpopulations

Gnomad4 AFR exome

AF:

0.975

Gnomad4 AMR exome

AF:

0.913

Gnomad4 ASJ exome

AF:

0.849

Gnomad4 EAS exome

AF:

0.988

Gnomad4 SAS exome

AF:

0.926

Gnomad4 FIN exome

AF:

0.810

Gnomad4 NFE exome

AF:

0.814

Gnomad4 OTH exome

AF:

0.852

GnomAD4 genome

AF:

0.871

AC:

132394

AN:

152068

Hom.:

58070

Cov.:

AF XY:

0.873

AC XY:

64872

AN XY:

74298

show subpopulations

Gnomad4 AFR

AF:

0.968

Gnomad4 AMR

AF:

0.880

Gnomad4 ASJ

AF:

0.856

Gnomad4 EAS

AF:

0.978

Gnomad4 SAS

AF:

0.932

Gnomad4 FIN

AF:

0.808

Gnomad4 NFE

AF:

0.807

Gnomad4 OTH

AF:

0.878

Alfa

AF:

0.816

Hom.:

13045

Bravo

AF:

0.881

Asia WGS

AF:

0.965

AC:

3357

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

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

-0.55

CADD

Benign

5.2

DANN

Benign

0.81

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