Variant rs114717951 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001369.3(DNAH5):c.2053-23A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00706 in 1,592,814 control chromosomes in the GnomAD database, including 119 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.0051 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0073 ( 117 hom. )

Consequence

DNAH5
NM_001369.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.00300

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:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

This place is a probable branch point but likely benign (scored 2 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 5-13900435-T-G is Benign according to our data. Variant chr5-13900435-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 258008.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00509 (775/152320) while in subpopulation SAS AF= 0.03 (145/4828). AF 95% confidence interval is 0.0261. There are 2 homozygotes in gnomad4. There are 418 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH5	NM_001369.3 linkuse as main transcript	c.2053-23A>C		intron_variant		ENST00000265104.5

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris
DNAH5	ENST00000265104.5 linkuse as main transcript	c.2053-23A>C	intron_variant		1	NM_001369.3	P4
	ENST00000503244.2 linkuse as main transcript	n.3311T>G	non_coding_transcript_exon_variant	3/3	4
DNAH5	ENST00000681290.1 linkuse as main transcript	c.2008-23A>C	intron_variant				A1
	ENST00000637153.1 linkuse as main transcript	n.3271T>G	non_coding_transcript_exon_variant	3/3	5

Frequencies

GnomAD3 genomes

AF:

0.00512

AC:

780

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000941

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00759

Gnomad ASJ

AF:

0.0138

Gnomad EAS

AF:

0.00231

Gnomad SAS

AF:

0.0306

Gnomad FIN

AF:

0.00122

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.00560

Gnomad OTH

AF:

0.00621

GnomAD3 exomes

AF:

0.00958

AC:

2382

AN:

248738

Hom.:

AF XY:

0.0111

AC XY:

1499

AN XY:

134720

show subpopulations

Gnomad AFR exome

AF:

0.000567

Gnomad AMR exome

AF:

0.00528

Gnomad ASJ exome

AF:

0.0142

Gnomad EAS exome

AF:

0.00220

Gnomad SAS exome

AF:

0.0368

Gnomad FIN exome

AF:

0.00301

Gnomad NFE exome

AF:

0.00658

Gnomad OTH exome

AF:

0.0139

GnomAD4 exome

AF:

0.00727

AC:

10478

AN:

1440494

Hom.:

117

Cov.:

AF XY:

0.00843

AC XY:

6051

AN XY:

718114

show subpopulations

Gnomad4 AFR exome

AF:

0.00212

Gnomad4 AMR exome

AF:

0.00546

Gnomad4 ASJ exome

AF:

0.0139

Gnomad4 EAS exome

AF:

0.00116

Gnomad4 SAS exome

AF:

0.0375

Gnomad4 FIN exome

AF:

0.00300

Gnomad4 NFE exome

AF:

0.00512

Gnomad4 OTH exome

AF:

0.00929

GnomAD4 genome

AF:

0.00509

AC:

775

AN:

152320

Hom.:

Cov.:

AF XY:

0.00561

AC XY:

418

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.000938

Gnomad4 AMR

AF:

0.00758

Gnomad4 ASJ

AF:

0.0138

Gnomad4 EAS

AF:

0.00231

Gnomad4 SAS

AF:

0.0300

Gnomad4 FIN

AF:

0.00122

Gnomad4 NFE

AF:

0.00560

Gnomad4 OTH

AF:

0.00568

Alfa

AF:

0.00767

Hom.:

Bravo

AF:

0.00465

Asia WGS

AF:

0.0170

AC:

AN:

3476

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 18, 2020

- -

Primary ciliary dyskinesia 3

Benign:1

Benign, criteria provided, single submitter

clinical testing

Pars Genome Lab

Jun 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.64

DANN

Benign

0.46

La Branchor

0.54

BranchPoint Hunter

2.0

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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