Variant 5-13841918-CAAAAAAAAAA-CAAAAAAAAAAA details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6BA1

The NM_001369.3(DNAH5):c.5272-15_5272-14insT variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.49 ( 12437 hom., cov: 0)

Exomes 𝑓: 0.15 ( 97 hom. )

Consequence

DNAH5
NM_001369.3 splice_polypyrimidine_tract, intron

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:2

Conservation

PhyloP100: 0.617

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP6

Variant 5-13841918-C-CA is Benign according to our data. Variant chr5-13841918-C-CA is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 351094.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=1}.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.554 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.5272-15_5272-14insT		splice_polypyrimidine_tract_variant, intron_variant		ENST00000265104.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH5	ENST00000265104.5 linkuse as main transcript	c.5272-15_5272-14insT		splice_polypyrimidine_tract_variant, intron_variant		1	NM_001369.3	P4
DNAH5	ENST00000681290.1 linkuse as main transcript	c.5227-15_5227-14insT		splice_polypyrimidine_tract_variant, intron_variant				A1

Frequencies

GnomAD3 genomes

AF:

0.487

AC:

50848

AN:

104496

Hom.:

12441

Cov.:

show subpopulations

Gnomad AFR

AF:

0.355

Gnomad AMI

AF:

0.467

Gnomad AMR

AF:

0.516

Gnomad ASJ

AF:

0.524

Gnomad EAS

AF:

0.212

Gnomad SAS

AF:

0.554

Gnomad FIN

AF:

0.479

Gnomad MID

AF:

0.526

Gnomad NFE

AF:

0.559

Gnomad OTH

AF:

0.505

GnomAD4 exome

AF:

0.147

AC:

69437

AN:

473344

Hom.:

Cov.:

AF XY:

0.148

AC XY:

37774

AN XY:

255706

show subpopulations

Gnomad4 AFR exome

AF:

0.0990

Gnomad4 AMR exome

AF:

0.126

Gnomad4 ASJ exome

AF:

0.129

Gnomad4 EAS exome

AF:

0.0886

Gnomad4 SAS exome

AF:

0.166

Gnomad4 FIN exome

AF:

0.169

Gnomad4 NFE exome

AF:

0.151

Gnomad4 OTH exome

AF:

0.144

GnomAD4 genome

AF:

0.486

AC:

50832

AN:

104490

Hom.:

12437

Cov.:

AF XY:

0.479

AC XY:

22584

AN XY:

47158

show subpopulations

Gnomad4 AFR

AF:

0.355

Gnomad4 AMR

AF:

0.515

Gnomad4 ASJ

AF:

0.524

Gnomad4 EAS

AF:

0.212

Gnomad4 SAS

AF:

0.555

Gnomad4 FIN

AF:

0.479

Gnomad4 NFE

AF:

0.559

Gnomad4 OTH

AF:

0.504

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:2

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Primary ciliary dyskinesia

Uncertain:1Benign:1

Likely benign, criteria provided, single submitter	clinical testing	Ambry Genetics	Sep 03, 2014	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
Uncertain significance, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Aug 22, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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