Variant 17-78453423-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.10449C>G(p.Thr3483=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.543 in 1,613,054 control chromosomes in the GnomAD database, including 241,327 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.49 ( 19086 hom., cov: 34)

Exomes 𝑓: 0.55 ( 222241 hom. )

Consequence

DNAH17
NM_173628.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.319

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=-0.51).

BP6

Variant 17-78453423-G-C is Benign according to our data. Variant chr17-78453423-G-C is described in ClinVar as [Benign]. Clinvar id is 402676.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.319 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.616 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.10449C>G	p.Thr3483=	synonymous_variant	65/81	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.10449C>G	p.Thr3483=	synonymous_variant	65/81	5	NM_173628.4	ENSP00000374490	P1	Q9UFH2-1
DNAH17	ENST00000586052.5 linkuse as main transcript	n.3734C>G		non_coding_transcript_exon_variant	20/35	5
DNAH17	ENST00000592152.1 linkuse as main transcript	n.796C>G		non_coding_transcript_exon_variant	4/5	5
DNAH17	ENST00000591369.5 linkuse as main transcript	c.2052C>G	p.Thr684=	synonymous_variant, NMD_transcript_variant	12/28	5		ENSP00000466150

Frequencies

GnomAD3 genomes

AF:

0.490

AC:

74539

AN:

152064

Hom.:

19072

Cov.:

show subpopulations

Gnomad AFR

AF:

0.344

Gnomad AMI

AF:

0.451

Gnomad AMR

AF:

0.507

Gnomad ASJ

AF:

0.602

Gnomad EAS

AF:

0.635

Gnomad SAS

AF:

0.412

Gnomad FIN

AF:

0.538

Gnomad MID

AF:

0.633

Gnomad NFE

AF:

0.556

Gnomad OTH

AF:

0.527

GnomAD3 exomes

AF:

0.521

AC:

130131

AN:

249610

Hom.:

34668

AF XY:

0.524

AC XY:

70720

AN XY:

134946

show subpopulations

Gnomad AFR exome

AF:

0.326

Gnomad AMR exome

AF:

0.484

Gnomad ASJ exome

AF:

0.585

Gnomad EAS exome

AF:

0.641

Gnomad SAS exome

AF:

0.415

Gnomad FIN exome

AF:

0.537

Gnomad NFE exome

AF:

0.559

Gnomad OTH exome

AF:

0.563

GnomAD4 exome

AF:

0.548

AC:

801073

AN:

1460872

Hom.:

222241

Cov.:

AF XY:

0.545

AC XY:

396122

AN XY:

726668

show subpopulations

Gnomad4 AFR exome

AF:

0.336

Gnomad4 AMR exome

AF:

0.486

Gnomad4 ASJ exome

AF:

0.588

Gnomad4 EAS exome

AF:

0.605

Gnomad4 SAS exome

AF:

0.417

Gnomad4 FIN exome

AF:

0.542

Gnomad4 NFE exome

AF:

0.564

Gnomad4 OTH exome

AF:

0.553

GnomAD4 genome

AF:

0.490

AC:

74573

AN:

152182

Hom.:

19086

Cov.:

AF XY:

0.489

AC XY:

36414

AN XY:

74396

show subpopulations

Gnomad4 AFR

AF:

0.343

Gnomad4 AMR

AF:

0.507

Gnomad4 ASJ

AF:

0.602

Gnomad4 EAS

AF:

0.634

Gnomad4 SAS

AF:

0.412

Gnomad4 FIN

AF:

0.538

Gnomad4 NFE

AF:

0.556

Gnomad4 OTH

AF:

0.532

Alfa

AF:

0.544

Hom.:

7419

Bravo

AF:

0.485

Asia WGS

AF:

0.506

AC:

1761

AN:

3478

EpiCase

AF:

0.562

EpiControl

AF:

0.582

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

-0.51

CADD

Benign

4.4

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