rs30175

Positions:

Variant summary

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

The ENST00000265104.5(DNAH5):c.12910-11C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.411 in 1,612,616 control chromosomes in the GnomAD database, including 137,296 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.39 ( 11943 hom., cov: 32)

Exomes 𝑓: 0.41 ( 125353 hom. )

Consequence

DNAH5
ENST00000265104.5 splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00001917

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: 0.717

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=-0.9).

BP6

Variant 5-13714631-G-A is Benign according to our data. Variant chr5-13714631-G-A is described in ClinVar as [Benign]. Clinvar id is 163133.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-13714631-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.435 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.12910-11C>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000265104.5	NP_001360.1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris
DNAH5	ENST00000265104.5 linkuse as main transcript	c.12910-11C>T	splice_polypyrimidine_tract_variant, intron_variant		1	NM_001369.3	ENSP00000265104	P4
DNAH5	ENST00000681290.1 linkuse as main transcript	c.12865-11C>T	splice_polypyrimidine_tract_variant, intron_variant				ENSP00000505288	A1
DNAH5	ENST00000683611.1 linkuse as main transcript	n.232C>T	non_coding_transcript_exon_variant	1/5

Frequencies

GnomAD3 genomes

AF:

0.394

AC:

59889

AN:

151896

Hom.:

11928

Cov.:

show subpopulations

Gnomad AFR

AF:

0.367

Gnomad AMI

AF:

0.438

Gnomad AMR

AF:

0.410

Gnomad ASJ

AF:

0.412

Gnomad EAS

AF:

0.431

Gnomad SAS

AF:

0.450

Gnomad FIN

AF:

0.316

Gnomad MID

AF:

0.437

Gnomad NFE

AF:

0.411

Gnomad OTH

AF:

0.399

GnomAD3 exomes

AF:

0.411

AC:

102830

AN:

250040

Hom.:

21338

AF XY:

0.414

AC XY:

55883

AN XY:

135122

show subpopulations

Gnomad AFR exome

AF:

0.367

Gnomad AMR exome

AF:

0.439

Gnomad ASJ exome

AF:

0.416

Gnomad EAS exome

AF:

0.412

Gnomad SAS exome

AF:

0.453

Gnomad FIN exome

AF:

0.326

Gnomad NFE exome

AF:

0.413

Gnomad OTH exome

AF:

0.415

GnomAD4 exome

AF:

0.413

AC:

603156

AN:

1460600

Hom.:

125353

Cov.:

AF XY:

0.414

AC XY:

300768

AN XY:

726608

show subpopulations

Gnomad4 AFR exome

AF:

0.358

Gnomad4 AMR exome

AF:

0.434

Gnomad4 ASJ exome

AF:

0.406

Gnomad4 EAS exome

AF:

0.400

Gnomad4 SAS exome

AF:

0.453

Gnomad4 FIN exome

AF:

0.331

Gnomad4 NFE exome

AF:

0.415

Gnomad4 OTH exome

AF:

0.414

GnomAD4 genome

AF:

0.394

AC:

59950

AN:

152016

Hom.:

11943

Cov.:

AF XY:

0.390

AC XY:

28945

AN XY:

74294

show subpopulations

Gnomad4 AFR

AF:

0.367

Gnomad4 AMR

AF:

0.410

Gnomad4 ASJ

AF:

0.412

Gnomad4 EAS

AF:

0.431

Gnomad4 SAS

AF:

0.450

Gnomad4 FIN

AF:

0.316

Gnomad4 NFE

AF:

0.411

Gnomad4 OTH

AF:

0.402

Alfa

AF:

0.401

Hom.:

13909

Bravo

AF:

0.400

Asia WGS

AF:

0.447

AC:

1556

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Feb 21, 2013	12910-11C>T in intron 74 of DNAH5: This variant is not expected to have clinical significance because it has been identified in 42.3% (3635/8600) of European Am erican chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS; dbSNP rs30175). -
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	-	- -

Primary ciliary dyskinesia 3

Benign:3

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 30, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Pars Genome Lab	Jun 15, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 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. -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

-0.90

CADD

Benign

1.2

DANN

Benign

0.48

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000019

dbscSNV1_RF

Benign

0.0

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