Variant rs35621834 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.3834+40C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 1,546,678 control chromosomes in the GnomAD database, including 12,573 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.10 ( 965 hom., cov: 32)

Exomes 𝑓: 0.12 ( 11608 hom. )

Consequence

DNAH5
NM_001369.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.17

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:

(HGNC:):

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=-0.77).

BP6

Variant 5-13870727-G-A is Benign according to our data. Variant chr5-13870727-G-A is described in ClinVar as [Benign]. Clinvar id is 258022.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.135 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.3834+40C>T		intron_variant		ENST00000265104.5

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris
DNAH5	ENST00000265104.5 linkuse as main transcript	c.3834+40C>T	intron_variant	1	NM_001369.3	P4
	ENST00000503244.2 linkuse as main transcript	n.253+10172G>A	intron_variant, non_coding_transcript_variant	4
DNAH5	ENST00000681290.1 linkuse as main transcript	c.3789+40C>T	intron_variant			A1
	ENST00000637153.1 linkuse as main transcript	n.213+10212G>A	intron_variant, non_coding_transcript_variant	5

Frequencies

GnomAD3 genomes

AF:

0.104

AC:

15809

AN:

151968

Hom.:

964

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0572

Gnomad AMI

AF:

0.0559

Gnomad AMR

AF:

0.0669

Gnomad ASJ

AF:

0.0677

Gnomad EAS

AF:

0.103

Gnomad SAS

AF:

0.0466

Gnomad FIN

AF:

0.173

Gnomad MID

AF:

0.0728

Gnomad NFE

AF:

0.137

Gnomad OTH

AF:

0.0986

GnomAD3 exomes

AF:

0.103

AC:

24392

AN:

237060

Hom.:

1452

AF XY:

0.103

AC XY:

13220

AN XY:

128260

show subpopulations

Gnomad AFR exome

AF:

0.0498

Gnomad AMR exome

AF:

0.0461

Gnomad ASJ exome

AF:

0.0723

Gnomad EAS exome

AF:

0.0983

Gnomad SAS exome

AF:

0.0488

Gnomad FIN exome

AF:

0.168

Gnomad NFE exome

AF:

0.134

Gnomad OTH exome

AF:

0.110

GnomAD4 exome

AF:

0.125

AC:

173851

AN:

1394592

Hom.:

11608

Cov.:

AF XY:

0.122

AC XY:

85301

AN XY:

696856

show subpopulations

Gnomad4 AFR exome

AF:

0.0535

Gnomad4 AMR exome

AF:

0.0502

Gnomad4 ASJ exome

AF:

0.0722

Gnomad4 EAS exome

AF:

0.0915

Gnomad4 SAS exome

AF:

0.0495

Gnomad4 FIN exome

AF:

0.169

Gnomad4 NFE exome

AF:

0.137

Gnomad4 OTH exome

AF:

0.116

GnomAD4 genome

AF:

0.104

AC:

15818

AN:

152086

Hom.:

965

Cov.:

AF XY:

0.102

AC XY:

7571

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.0572

Gnomad4 AMR

AF:

0.0669

Gnomad4 ASJ

AF:

0.0677

Gnomad4 EAS

AF:

0.104

Gnomad4 SAS

AF:

0.0471

Gnomad4 FIN

AF:

0.173

Gnomad4 NFE

AF:

0.137

Gnomad4 OTH

AF:

0.0980

Alfa

AF:

0.115

Hom.:

202

Bravo

AF:

0.0936

Asia WGS

AF:

0.0830

AC:

289

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 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

-0.77

CADD

Benign

9.8

DANN

Benign

0.72

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