Variant rs35925547 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.975+30A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.272 in 1,613,530 control chromosomes in the GnomAD database, including 62,285 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 4585 hom., cov: 32)

Exomes 𝑓: 0.28 ( 57700 hom. )

Consequence

DNAH5
NM_001369.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.172

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

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 5-13919146-T-G is Benign according to our data. Variant chr5-13919146-T-G is described in ClinVar as [Benign]. Clinvar id is 258072.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.331 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH5	NM_001369.3 linkuse as main transcript	c.975+30A>C		intron_variant		ENST00000265104.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH5	ENST00000265104.5 linkuse as main transcript	c.975+30A>C		intron_variant		1	NM_001369.3	P4

Frequencies

GnomAD3 genomes

AF:

0.228

AC:

34635

AN:

152070

Hom.:

4577

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0923

Gnomad AMI

AF:

0.374

Gnomad AMR

AF:

0.256

Gnomad ASJ

AF:

0.311

Gnomad EAS

AF:

0.0891

Gnomad SAS

AF:

0.343

Gnomad FIN

AF:

0.323

Gnomad MID

AF:

0.199

Gnomad NFE

AF:

0.285

Gnomad OTH

AF:

0.245

GnomAD3 exomes

AF:

0.261

AC:

65253

AN:

250400

Hom.:

9251

AF XY:

0.269

AC XY:

36415

AN XY:

135412

show subpopulations

Gnomad AFR exome

AF:

0.0911

Gnomad AMR exome

AF:

0.248

Gnomad ASJ exome

AF:

0.307

Gnomad EAS exome

AF:

0.0827

Gnomad SAS exome

AF:

0.353

Gnomad FIN exome

AF:

0.310

Gnomad NFE exome

AF:

0.279

Gnomad OTH exome

AF:

0.250

GnomAD4 exome

AF:

0.276

AC:

403602

AN:

1461344

Hom.:

57700

Cov.:

AF XY:

0.279

AC XY:

202626

AN XY:

727016

show subpopulations

Gnomad4 AFR exome

AF:

0.0839

Gnomad4 AMR exome

AF:

0.246

Gnomad4 ASJ exome

AF:

0.311

Gnomad4 EAS exome

AF:

0.0953

Gnomad4 SAS exome

AF:

0.348

Gnomad4 FIN exome

AF:

0.301

Gnomad4 NFE exome

AF:

0.283

Gnomad4 OTH exome

AF:

0.262

GnomAD4 genome

AF:

0.228

AC:

34670

AN:

152186

Hom.:

4585

Cov.:

AF XY:

0.231

AC XY:

17182

AN XY:

74388

show subpopulations

Gnomad4 AFR

AF:

0.0921

Gnomad4 AMR

AF:

0.257

Gnomad4 ASJ

AF:

0.311

Gnomad4 EAS

AF:

0.0893

Gnomad4 SAS

AF:

0.345

Gnomad4 FIN

AF:

0.323

Gnomad4 NFE

AF:

0.285

Gnomad4 OTH

AF:

0.250

Alfa

AF:

0.273

Hom.:

1170

Bravo

AF:

0.214

Asia WGS

AF:

0.228

AC:

795

AN:

3476

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 11, 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

-0.83

CADD

Benign

2.1

DANN

Benign

0.51

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