Variant rs17203442 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001369.3(DNAH5):c.12034-24T>C variant causes a intron change. The variant allele was found at a frequency of 0.13 in 1,613,384 control chromosomes in the GnomAD database, including 15,659 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.11 ( 1181 hom., cov: 33)

Exomes 𝑓: 0.13 ( 14478 hom. )

Consequence

DNAH5
NM_001369.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 5.20

Variant links:

Genes affected

DNAH5 (HGNC:2950): (dynein axonemal heavy chain 5) This gene encodes a dynein protein, which is part of a microtubule-associated motor protein complex consisting of heavy, light, and intermediate chains. This protein is an axonemal heavy chain dynein. It functions as a force-generating protein with ATPase activity, whereby the release of ADP is thought to produce the force-producing power stroke. Mutations in this gene cause primary ciliary dyskinesia type 3, as well as Kartagener syndrome, which are both diseases due to ciliary defects. [provided by RefSeq, Oct 2009]

DNAH5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

This place is a probable branch point but rather VUS (scored 5 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP6

Variant 5-13721269-A-G is Benign according to our data. Variant chr5-13721269-A-G is described in ClinVar as [Benign]. Clinvar id is 257989.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-13721269-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.145 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH5	NM_001369.3 linkuse as main transcript	c.12034-24T>C		intron_variant		ENST00000265104.5	NP_001360.1	Q8TE73

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAH5	ENST00000265104.5 linkuse as main transcript	c.12034-24T>C		intron_variant		1	NM_001369.3	ENSP00000265104.4		Q8TE73
DNAH5	ENST00000681290.1 linkuse as main transcript	c.11989-24T>C		intron_variant				ENSP00000505288.1		A0A7P0Z455

Frequencies

GnomAD3 genomes

AF:

0.108

AC:

16404

AN:

152158

Hom.:

1181

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0334

Gnomad AMI

AF:

0.173

Gnomad AMR

AF:

0.102

Gnomad ASJ

AF:

0.146

Gnomad EAS

AF:

0.00404

Gnomad SAS

AF:

0.0286

Gnomad FIN

AF:

0.219

Gnomad MID

AF:

0.0981

Gnomad NFE

AF:

0.148

Gnomad OTH

AF:

0.115

GnomAD3 exomes

AF:

0.108

AC:

26860

AN:

249706

Hom.:

1915

AF XY:

0.106

AC XY:

14346

AN XY:

135168

show subpopulations

Gnomad AFR exome

AF:

0.0295

Gnomad AMR exome

AF:

0.0672

Gnomad ASJ exome

AF:

0.141

Gnomad EAS exome

AF:

0.00448

Gnomad SAS exome

AF:

0.0266

Gnomad FIN exome

AF:

0.209

Gnomad NFE exome

AF:

0.147

Gnomad OTH exome

AF:

0.123

GnomAD4 exome

AF:

0.133

AC:

194086

AN:

1461108

Hom.:

14478

Cov.:

AF XY:

0.130

AC XY:

94712

AN XY:

726912

show subpopulations

Gnomad4 AFR exome

AF:

0.0282

Gnomad4 AMR exome

AF:

0.0716

Gnomad4 ASJ exome

AF:

0.143

Gnomad4 EAS exome

AF:

0.00219

Gnomad4 SAS exome

AF:

0.0272

Gnomad4 FIN exome

AF:

0.204

Gnomad4 NFE exome

AF:

0.149

Gnomad4 OTH exome

AF:

0.117

GnomAD4 genome

AF:

0.108

AC:

16399

AN:

152276

Hom.:

1181

Cov.:

AF XY:

0.109

AC XY:

8098

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.0334

Gnomad4 AMR

AF:

0.102

Gnomad4 ASJ

AF:

0.146

Gnomad4 EAS

AF:

0.00405

Gnomad4 SAS

AF:

0.0288

Gnomad4 FIN

AF:

0.219

Gnomad4 NFE

AF:

0.148

Gnomad4 OTH

AF:

0.113

Alfa

AF:

0.136

Hom.:

2999

Bravo

AF:

0.0968

Asia WGS

AF:

0.0250

AC:

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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Primary ciliary dyskinesia 3

Benign:1

Benign, criteria provided, single submitter

clinical testing

Pars Genome Lab

Jun 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

DANN

Benign

0.54

BranchPoint Hunter

5.0

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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