Variant rs2166337 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.13724-35T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.544 in 1,611,270 control chromosomes in the GnomAD database, including 239,576 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.55 ( 22763 hom., cov: 31)

Exomes 𝑓: 0.54 ( 216813 hom. )

Consequence

DNAH5
NM_001369.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.192

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 5-13692170-A-T is Benign according to our data. Variant chr5-13692170-A-T is described in ClinVar as [Benign]. Clinvar id is 258001.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.557 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.13724-35T>A		intron_variant		ENST00000265104.5	NP_001360.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris
DNAH5	ENST00000265104.5 linkuse as main transcript	c.13724-35T>A	intron_variant	1	NM_001369.3	ENSP00000265104	P4
DNAH5	ENST00000681290.1 linkuse as main transcript	c.13679-35T>A	intron_variant			ENSP00000505288	A1
DNAH5	ENST00000683611.1 linkuse as main transcript	n.1057-35T>A	intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.545

AC:

82803

AN:

151900

Hom.:

22737

Cov.:

show subpopulations

Gnomad AFR

AF:

0.563

Gnomad AMI

AF:

0.588

Gnomad AMR

AF:

0.524

Gnomad ASJ

AF:

0.555

Gnomad EAS

AF:

0.450

Gnomad SAS

AF:

0.439

Gnomad FIN

AF:

0.545

Gnomad MID

AF:

0.532

Gnomad NFE

AF:

0.553

Gnomad OTH

AF:

0.551

GnomAD3 exomes

AF:

0.523

AC:

128841

AN:

246408

Hom.:

34001

AF XY:

0.518

AC XY:

69237

AN XY:

133670

show subpopulations

Gnomad AFR exome

AF:

0.564

Gnomad AMR exome

AF:

0.508

Gnomad ASJ exome

AF:

0.544

Gnomad EAS exome

AF:

0.429

Gnomad SAS exome

AF:

0.436

Gnomad FIN exome

AF:

0.544

Gnomad NFE exome

AF:

0.555

Gnomad OTH exome

AF:

0.532

GnomAD4 exome

AF:

0.543

AC:

793072

AN:

1459252

Hom.:

216813

Cov.:

AF XY:

0.540

AC XY:

391790

AN XY:

725950

show subpopulations

Gnomad4 AFR exome

AF:

0.555

Gnomad4 AMR exome

AF:

0.509

Gnomad4 ASJ exome

AF:

0.541

Gnomad4 EAS exome

AF:

0.410

Gnomad4 SAS exome

AF:

0.437

Gnomad4 FIN exome

AF:

0.541

Gnomad4 NFE exome

AF:

0.558

Gnomad4 OTH exome

AF:

0.535

GnomAD4 genome

AF:

0.545

AC:

82891

AN:

152018

Hom.:

22763

Cov.:

AF XY:

0.540

AC XY:

40112

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.563

Gnomad4 AMR

AF:

0.524

Gnomad4 ASJ

AF:

0.555

Gnomad4 EAS

AF:

0.450

Gnomad4 SAS

AF:

0.439

Gnomad4 FIN

AF:

0.545

Gnomad4 NFE

AF:

0.553

Gnomad4 OTH

AF:

0.554

Alfa

AF:

0.541

Hom.:

4133

Bravo

AF:

0.547

Asia WGS

AF:

0.481

AC:

1674

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

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	- -

Primary ciliary dyskinesia 3

Benign:2

Benign, criteria provided, single submitter	clinical testing	Pars Genome Lab	Jun 15, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 30, 2021	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

2.9

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