Variant rs4701988 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.5114+22A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.385 in 1,608,968 control chromosomes in the GnomAD database, including 122,568 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.35 ( 9747 hom., cov: 33)

Exomes 𝑓: 0.39 ( 112821 hom. )

Consequence

DNAH5
NM_001369.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.858

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=-0.78).

BP6

Variant 5-13850630-T-A is Benign according to our data. Variant chr5-13850630-T-A is described in ClinVar as [Benign]. Clinvar id is 258038.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.563 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.5114+22A>T		intron_variant		ENST00000265104.5	NP_001360.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAH5	ENST00000265104.5 linkuse as main transcript	c.5114+22A>T		intron_variant		1	NM_001369.3	ENSP00000265104	P4
DNAH5	ENST00000681290.1 linkuse as main transcript	c.5069+22A>T		intron_variant				ENSP00000505288	A1

Frequencies

GnomAD3 genomes

AF:

0.347

AC:

52752

AN:

152028

Hom.:

9750

Cov.:

show subpopulations

Gnomad AFR

AF:

0.210

Gnomad AMI

AF:

0.453

Gnomad AMR

AF:

0.406

Gnomad ASJ

AF:

0.484

Gnomad EAS

AF:

0.580

Gnomad SAS

AF:

0.318

Gnomad FIN

AF:

0.336

Gnomad MID

AF:

0.453

Gnomad NFE

AF:

0.393

Gnomad OTH

AF:

0.387

GnomAD3 exomes

AF:

0.388

AC:

97255

AN:

250900

Hom.:

19873

AF XY:

0.388

AC XY:

52647

AN XY:

135624

show subpopulations

Gnomad AFR exome

AF:

0.206

Gnomad AMR exome

AF:

0.400

Gnomad ASJ exome

AF:

0.479

Gnomad EAS exome

AF:

0.595

Gnomad SAS exome

AF:

0.307

Gnomad FIN exome

AF:

0.342

Gnomad NFE exome

AF:

0.396

Gnomad OTH exome

AF:

0.422

GnomAD4 exome

AF:

0.389

AC:

566610

AN:

1456822

Hom.:

112821

Cov.:

AF XY:

0.388

AC XY:

281191

AN XY:

725124

show subpopulations

Gnomad4 AFR exome

AF:

0.200

Gnomad4 AMR exome

AF:

0.401

Gnomad4 ASJ exome

AF:

0.479

Gnomad4 EAS exome

AF:

0.584

Gnomad4 SAS exome

AF:

0.310

Gnomad4 FIN exome

AF:

0.348

Gnomad4 NFE exome

AF:

0.392

Gnomad4 OTH exome

AF:

0.397

GnomAD4 genome

AF:

0.347

AC:

52753

AN:

152146

Hom.:

9747

Cov.:

AF XY:

0.349

AC XY:

25938

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.210

Gnomad4 AMR

AF:

0.406

Gnomad4 ASJ

AF:

0.484

Gnomad4 EAS

AF:

0.580

Gnomad4 SAS

AF:

0.317

Gnomad4 FIN

AF:

0.336

Gnomad4 NFE

AF:

0.393

Gnomad4 OTH

AF:

0.386

Alfa

AF:

0.292

Hom.:

1204

Bravo

AF:

0.352

Asia WGS

AF:

0.410

AC:

1426

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	Apr 04, 2019	- -

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

-0.78

CADD

Benign

8.8

DANN

Benign

0.75

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