rs35732567

Variant summary

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

The NM_001369.3(DNAH5):c.7609+19C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.387 in 1,549,262 control chromosomes in the GnomAD database, including 117,563 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.38 ( 11042 hom., cov: 32)

Exomes 𝑓: 0.39 ( 106521 hom. )

Consequence

DNAH5
NM_001369.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.0950

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=-0.91).

BP6

Variant 5-13810040-G-A is Benign according to our data. Variant chr5-13810040-G-A is described in ClinVar as [Benign]. Clinvar id is 197516.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-13810040-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.607 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.7609+19C>T		intron_variant		ENST00000265104.5

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris
DNAH5	ENST00000265104.5 linkuse as main transcript	c.7609+19C>T	intron_variant	1	NM_001369.3	P4
DNAH5	ENST00000681290.1 linkuse as main transcript	c.7564+19C>T	intron_variant			A1
DNAH5	ENST00000512443.1 linkuse as main transcript	n.465+19C>T	intron_variant, non_coding_transcript_variant	3

Frequencies

GnomAD3 genomes

AF:

0.377

AC:

57223

AN:

151922

Hom.:

11038

Cov.:

show subpopulations

Gnomad AFR

AF:

0.325

Gnomad AMI

AF:

0.524

Gnomad AMR

AF:

0.399

Gnomad ASJ

AF:

0.367

Gnomad EAS

AF:

0.625

Gnomad SAS

AF:

0.345

Gnomad FIN

AF:

0.353

Gnomad MID

AF:

0.367

Gnomad NFE

AF:

0.388

Gnomad OTH

AF:

0.393

GnomAD3 exomes

AF:

0.393

AC:

60520

AN:

154048

Hom.:

12341

AF XY:

0.390

AC XY:

31848

AN XY:

81718

show subpopulations

Gnomad AFR exome

AF:

0.323

Gnomad AMR exome

AF:

0.399

Gnomad ASJ exome

AF:

0.356

Gnomad EAS exome

AF:

0.646

Gnomad SAS exome

AF:

0.339

Gnomad FIN exome

AF:

0.362

Gnomad NFE exome

AF:

0.384

Gnomad OTH exome

AF:

0.406

GnomAD4 exome

AF:

0.388

AC:

542739

AN:

1397226

Hom.:

106521

Cov.:

AF XY:

0.387

AC XY:

266642

AN XY:

689292

show subpopulations

Gnomad4 AFR exome

AF:

0.327

Gnomad4 AMR exome

AF:

0.406

Gnomad4 ASJ exome

AF:

0.359

Gnomad4 EAS exome

AF:

0.573

Gnomad4 SAS exome

AF:

0.342

Gnomad4 FIN exome

AF:

0.362

Gnomad4 NFE exome

AF:

0.389

Gnomad4 OTH exome

AF:

0.390

GnomAD4 genome

AF:

0.377

AC:

57252

AN:

152036

Hom.:

11042

Cov.:

AF XY:

0.376

AC XY:

27921

AN XY:

74302

show subpopulations

Gnomad4 AFR

AF:

0.325

Gnomad4 AMR

AF:

0.399

Gnomad4 ASJ

AF:

0.367

Gnomad4 EAS

AF:

0.625

Gnomad4 SAS

AF:

0.345

Gnomad4 FIN

AF:

0.353

Gnomad4 NFE

AF:

0.388

Gnomad4 OTH

AF:

0.389

Alfa

AF:

0.376

Hom.:

2213

Bravo

AF:

0.381

Asia WGS

AF:

0.450

AC:

1562

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Mar 16, 2016	- -

Primary ciliary dyskinesia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 11, 2018

- -

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

-0.91

Cadd

Benign

3.3

Dann

Benign

0.76

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