Variant 17-78476686-G-A 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.8040C>T(p.Leu2680=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.23 in 1,611,882 control chromosomes in the GnomAD database, including 51,979 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.34 ( 12352 hom., cov: 32)

Exomes 𝑓: 0.22 ( 39627 hom. )

Consequence

DNAH17
NM_173628.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.67

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=-0.72).

BP6

Variant 17-78476686-G-A is Benign according to our data. Variant chr17-78476686-G-A is described in ClinVar as [Benign]. Clinvar id is 402679.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.67 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.675 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.8040C>T	p.Leu2680=	synonymous_variant	52/81	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.8040C>T	p.Leu2680=	synonymous_variant	52/81	5	NM_173628.4	ENSP00000374490	P1	Q9UFH2-1
DNAH17	ENST00000586052.5 linkuse as main transcript	n.1511-827C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.344

AC:

52246

AN:

151914

Hom.:

12314

Cov.:

show subpopulations

Gnomad AFR

AF:

0.681

Gnomad AMI

AF:

0.182

Gnomad AMR

AF:

0.266

Gnomad ASJ

AF:

0.202

Gnomad EAS

AF:

0.282

Gnomad SAS

AF:

0.245

Gnomad FIN

AF:

0.207

Gnomad MID

AF:

0.263

Gnomad NFE

AF:

0.200

Gnomad OTH

AF:

0.323

GnomAD3 exomes

AF:

0.249

AC:

61240

AN:

246036

Hom.:

9284

AF XY:

0.243

AC XY:

32380

AN XY:

133442

show subpopulations

Gnomad AFR exome

AF:

0.695

Gnomad AMR exome

AF:

0.230

Gnomad ASJ exome

AF:

0.190

Gnomad EAS exome

AF:

0.289

Gnomad SAS exome

AF:

0.249

Gnomad FIN exome

AF:

0.206

Gnomad NFE exome

AF:

0.202

Gnomad OTH exome

AF:

0.229

GnomAD4 exome

AF:

0.218

AC:

318529

AN:

1459850

Hom.:

39627

Cov.:

AF XY:

0.217

AC XY:

157603

AN XY:

726002

show subpopulations

Gnomad4 AFR exome

AF:

0.696

Gnomad4 AMR exome

AF:

0.231

Gnomad4 ASJ exome

AF:

0.195

Gnomad4 EAS exome

AF:

0.242

Gnomad4 SAS exome

AF:

0.247

Gnomad4 FIN exome

AF:

0.207

Gnomad4 NFE exome

AF:

0.200

Gnomad4 OTH exome

AF:

0.242

GnomAD4 genome

AF:

0.344

AC:

52330

AN:

152032

Hom.:

12352

Cov.:

AF XY:

0.342

AC XY:

25397

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.682

Gnomad4 AMR

AF:

0.265

Gnomad4 ASJ

AF:

0.202

Gnomad4 EAS

AF:

0.281

Gnomad4 SAS

AF:

0.244

Gnomad4 FIN

AF:

0.207

Gnomad4 NFE

AF:

0.200

Gnomad4 OTH

AF:

0.324

Alfa

AF:

0.231

Hom.:

9376

Bravo

AF:

0.364

Asia WGS

AF:

0.306

AC:

1067

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

-0.72

CADD

Benign

0.094

DANN

Benign

0.57

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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