Variant rs1348691 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.6444+11C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.373 in 1,612,558 control chromosomes in the GnomAD database, including 114,252 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.40 ( 12277 hom., cov: 32)

Exomes 𝑓: 0.37 ( 101975 hom. )

Consequence

DNAH5
NM_001369.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 1.07

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=-0.82).

BP6

Variant 5-13829499-G-A is Benign according to our data. Variant chr5-13829499-G-A is described in ClinVar as [Benign]. Clinvar id is 163144.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-13829499-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.592 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.6444+11C>T		intron_variant		ENST00000265104.5

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris
DNAH5	ENST00000265104.5 linkuse as main transcript	c.6444+11C>T	intron_variant	1	NM_001369.3	P4
DNAH5	ENST00000681290.1 linkuse as main transcript	c.6399+11C>T	intron_variant			A1
DNAH5	ENST00000683090.1 linkuse as main transcript	n.1375+11C>T	intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.398

AC:

60510

AN:

151878

Hom.:

12261

Cov.:

show subpopulations

Gnomad AFR

AF:

0.461

Gnomad AMI

AF:

0.454

Gnomad AMR

AF:

0.383

Gnomad ASJ

AF:

0.366

Gnomad EAS

AF:

0.610

Gnomad SAS

AF:

0.333

Gnomad FIN

AF:

0.318

Gnomad MID

AF:

0.316

Gnomad NFE

AF:

0.366

Gnomad OTH

AF:

0.399

GnomAD3 exomes

AF:

0.384

AC:

96539

AN:

251110

Hom.:

19222

AF XY:

0.379

AC XY:

51449

AN XY:

135714

show subpopulations

Gnomad AFR exome

AF:

0.464

Gnomad AMR exome

AF:

0.373

Gnomad ASJ exome

AF:

0.362

Gnomad EAS exome

AF:

0.624

Gnomad SAS exome

AF:

0.331

Gnomad FIN exome

AF:

0.325

Gnomad NFE exome

AF:

0.366

Gnomad OTH exome

AF:

0.381

GnomAD4 exome

AF:

0.371

AC:

541690

AN:

1460562

Hom.:

101975

Cov.:

AF XY:

0.369

AC XY:

267884

AN XY:

726674

show subpopulations

Gnomad4 AFR exome

AF:

0.459

Gnomad4 AMR exome

AF:

0.377

Gnomad4 ASJ exome

AF:

0.359

Gnomad4 EAS exome

AF:

0.562

Gnomad4 SAS exome

AF:

0.330

Gnomad4 FIN exome

AF:

0.328

Gnomad4 NFE exome

AF:

0.366

Gnomad4 OTH exome

AF:

0.380

GnomAD4 genome

AF:

0.398

AC:

60563

AN:

151996

Hom.:

12277

Cov.:

AF XY:

0.396

AC XY:

29395

AN XY:

74288

show subpopulations

Gnomad4 AFR

AF:

0.461

Gnomad4 AMR

AF:

0.383

Gnomad4 ASJ

AF:

0.366

Gnomad4 EAS

AF:

0.609

Gnomad4 SAS

AF:

0.332

Gnomad4 FIN

AF:

0.318

Gnomad4 NFE

AF:

0.366

Gnomad4 OTH

AF:

0.397

Alfa

AF:

0.384

Hom.:

2483

Bravo

AF:

0.411

Asia WGS

AF:

0.454

AC:

1579

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Feb 21, 2013	6444+11C>T in intron 38 of DNAH5: This variant is not expected to have clinical significance because it is not located within the conserved splice consensus seq uence. It has been identified in 45.6% (2009/4406) of African American chromosom es from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs. washington.edu/EVS; dbSNP rs1348691). -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 11, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Primary ciliary dyskinesia 3

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Pars Genome Lab	Jun 15, 2021	- -

Primary ciliary dyskinesia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

DANN

Benign

0.59

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