Variant rs2271613 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.12681C>T(p.Tyr4227=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.72 in 1,607,814 control chromosomes in the GnomAD database, including 423,199 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.65 ( 34421 hom., cov: 32)

Exomes 𝑓: 0.73 ( 388778 hom. )

Consequence

DNAH17
NM_173628.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.423

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=-0.54).

BP6

Variant 17-78427016-G-A is Benign according to our data. Variant chr17-78427016-G-A is described in ClinVar as [Benign]. Clinvar id is 402672.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.423 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.915 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
DNAH17	NM_173628.4 linkuse as main transcript	c.12681C>T	p.Tyr4227=	synonymous_variant	78/81	ENST00000389840.7	NP_775899.3
DNAH17	XM_011525416.3 linkuse as main transcript	c.12693C>T	p.Tyr4231=	synonymous_variant	78/81		XP_011523718.1
DNAH17	XM_024451013.2 linkuse as main transcript	c.12549C>T	p.Tyr4183=	synonymous_variant	77/80		XP_024306781.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAH17	ENST00000389840.7 linkuse as main transcript	c.12681C>T	p.Tyr4227=	synonymous_variant	78/81	5	NM_173628.4	ENSP00000374490	P1	Q9UFH2-1

Frequencies

GnomAD3 genomes

AF:

0.654

AC:

99384

AN:

151968

Hom.:

34409

Cov.:

show subpopulations

Gnomad AFR

AF:

0.416

Gnomad AMI

AF:

0.797

Gnomad AMR

AF:

0.740

Gnomad ASJ

AF:

0.639

Gnomad EAS

AF:

0.937

Gnomad SAS

AF:

0.733

Gnomad FIN

AF:

0.831

Gnomad MID

AF:

0.611

Gnomad NFE

AF:

0.724

Gnomad OTH

AF:

0.662

GnomAD3 exomes

AF:

0.738

AC:

178120

AN:

241370

Hom.:

67146

AF XY:

0.737

AC XY:

96080

AN XY:

130402

show subpopulations

Gnomad AFR exome

AF:

0.408

Gnomad AMR exome

AF:

0.816

Gnomad ASJ exome

AF:

0.643

Gnomad EAS exome

AF:

0.933

Gnomad SAS exome

AF:

0.721

Gnomad FIN exome

AF:

0.823

Gnomad NFE exome

AF:

0.726

Gnomad OTH exome

AF:

0.710

GnomAD4 exome

AF:

0.727

AC:

1058665

AN:

1455728

Hom.:

388778

Cov.:

AF XY:

0.727

AC XY:

526203

AN XY:

723510

show subpopulations

Gnomad4 AFR exome

AF:

0.403

Gnomad4 AMR exome

AF:

0.808

Gnomad4 ASJ exome

AF:

0.640

Gnomad4 EAS exome

AF:

0.950

Gnomad4 SAS exome

AF:

0.720

Gnomad4 FIN exome

AF:

0.821

Gnomad4 NFE exome

AF:

0.725

Gnomad4 OTH exome

AF:

0.717

GnomAD4 genome

AF:

0.654

AC:

99423

AN:

152086

Hom.:

34421

Cov.:

AF XY:

0.663

AC XY:

49325

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.416

Gnomad4 AMR

AF:

0.740

Gnomad4 ASJ

AF:

0.639

Gnomad4 EAS

AF:

0.937

Gnomad4 SAS

AF:

0.732

Gnomad4 FIN

AF:

0.831

Gnomad4 NFE

AF:

0.724

Gnomad4 OTH

AF:

0.663

Alfa

AF:

0.709

Hom.:

88137

Bravo

AF:

0.638

Asia WGS

AF:

0.809

AC:

2809

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	Aug 21, 2018	- -
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

-0.54

CADD

Benign

1.1

DANN

Benign

0.93

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