Variant 5-13886135-CAAAAAAAAAA-CAAAAAAAAAAA details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_001369.3(DNAH5):c.2578-7dupT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.021 ( 65 hom., cov: 0)

Exomes 𝑓: 0.019 ( 8 hom. )

Consequence

DNAH5
NM_001369.3 splice_region, intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.0110

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:

ENSG00000251423 (HGNC:):

ENSG00000251423 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 5-13886135-C-CA is Benign according to our data. Variant chr5-13886135-C-CA is described in ClinVar as [Likely_benign]. Clinvar id is 1269037.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0602 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.2578-7dupT		splice_region_variant, intron_variant		ENST00000265104.5	NP_001360.1	Q8TE73

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
DNAH5	ENST00000265104.5 linkuse as main transcript	c.2578-7dupT	splice_region_variant, intron_variant	1	NM_001369.3	ENSP00000265104.4	Q8TE73
DNAH5	ENST00000681290.1 linkuse as main transcript	c.2533-7dupT	splice_region_variant, intron_variant			ENSP00000505288.1	A0A7P0Z455
ENSG00000251423	ENST00000503244.2 linkuse as main transcript	n.254-10435dupA	intron_variant	4
ENSG00000251423	ENST00000637153.1 linkuse as main transcript	n.214-10435dupA	intron_variant	5

Frequencies

GnomAD3 genomes

AF:

0.0209

AC:

2583

AN:

123802

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0625

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0105

Gnomad ASJ

AF:

0.00532

Gnomad EAS

AF:

0.0109

Gnomad SAS

AF:

0.0165

Gnomad FIN

AF:

0.000835

Gnomad MID

AF:

0.0273

Gnomad NFE

AF:

0.00311

Gnomad OTH

AF:

0.0218

GnomAD3 exomes

AF:

0.0376

AC:

2316

AN:

61536

Hom.:

AF XY:

0.0361

AC XY:

1132

AN XY:

31394

show subpopulations

Gnomad AFR exome

AF:

0.0531

Gnomad AMR exome

AF:

0.0362

Gnomad ASJ exome

AF:

0.0308

Gnomad EAS exome

AF:

0.0975

Gnomad SAS exome

AF:

0.0225

Gnomad FIN exome

AF:

0.0183

Gnomad NFE exome

AF:

0.0312

Gnomad OTH exome

AF:

0.0319

GnomAD4 exome

AF:

0.0188

AC:

22720

AN:

1205682

Hom.:

Cov.:

AF XY:

0.0188

AC XY:

11187

AN XY:

595948

show subpopulations

Gnomad4 AFR exome

AF:

0.0428

Gnomad4 AMR exome

AF:

0.0253

Gnomad4 ASJ exome

AF:

0.0222

Gnomad4 EAS exome

AF:

0.0436

Gnomad4 SAS exome

AF:

0.0240

Gnomad4 FIN exome

AF:

0.0162

Gnomad4 NFE exome

AF:

0.0166

Gnomad4 OTH exome

AF:

0.0221

GnomAD4 genome

AF:

0.0209

AC:

2583

AN:

123780

Hom.:

Cov.:

AF XY:

0.0206

AC XY:

1211

AN XY:

58676

show subpopulations

Gnomad4 AFR

AF:

0.0624

Gnomad4 AMR

AF:

0.0105

Gnomad4 ASJ

AF:

0.00532

Gnomad4 EAS

AF:

0.0109

Gnomad4 SAS

AF:

0.0164

Gnomad4 FIN

AF:

0.000835

Gnomad4 NFE

AF:

0.00311

Gnomad4 OTH

AF:

0.0217

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Primary ciliary dyskinesia

Benign:2

Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Sep 27, 2019	- -
Likely benign, criteria provided, single submitter	clinical testing	Ambry Genetics	Aug 07, 2015	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. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 15, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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