rs114717951

Variant names:

Variant summary

Our verdict is Benign. The variant received -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:4

Conservation

PhyloP100: -0.00300

Publications

2 publications found

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 Gene-Disease associations (from GenCC):

primary ciliary dyskinesia 3
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P, ClinGen
primary ciliary dyskinesia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

DNAH5 links:

ENSG00000251423 (HGNC:40187):

ENSG00000251423 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 2 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 2 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH5	NM_001369.3 link	c.2053-23A>C		intron_variant	Intron 14 of 78	ENST00000265104.5	NP_001360.1	Q8TE73

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
DNAH5	ENST00000265104.5 link	c.2053-23A>C	intron_variant	Intron 14 of 78	1	NM_001369.3	ENSP00000265104.4	Q8TE73
ENSG00000251423	ENST00000503244.2 link	n.3311T>G	non_coding_transcript_exon_variant	Exon 3 of 3	4
ENSG00000251423	ENST00000637153.1 link	n.3271T>G	non_coding_transcript_exon_variant	Exon 3 of 3	5
DNAH5	ENST00000681290.1 link	c.2008-23A>C	intron_variant	Intron 14 of 78			ENSP00000505288.1	A0A7P0Z455

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

GnomAD2 exomes

AF:

0.00958

AC:

2382

AN:

248738

AF XY:

0.0111

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 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

African (AFR)

AF:

0.00212

AC:

AN:

33048

American (AMR)

AF:

0.00546

AC:

244

AN:

44694

Ashkenazi Jewish (ASJ)

AF:

0.0139

AC:

361

AN:

25978

East Asian (EAS)

AF:

0.00116

AC:

AN:

39514

South Asian (SAS)

AF:

0.0375

AC:

3214

AN:

85774

European-Finnish (FIN)

AF:

0.00300

AC:

160

AN:

53322

Middle Eastern (MID)

AF:

0.0410

AC:

232

AN:

5656

European-Non Finnish (NFE)

AF:

0.00512

AC:

5597

AN:

1092858

Other (OTH)

AF:

0.00929

AC:

554

AN:

59650

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

488

976

1463

1951

2439

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00509

AC:

775

AN:

152320

Hom.:

Cov.:

AF XY:

0.00561

AC XY:

418

AN XY:

74492

show subpopulations

African (AFR)

AF:

0.000938

AC:

AN:

41566

American (AMR)

AF:

0.00758

AC:

116

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0138

AC:

AN:

3468

East Asian (EAS)

AF:

0.00231

AC:

AN:

5186

South Asian (SAS)

AF:

0.0300

AC:

145

AN:

4828

European-Finnish (FIN)

AF:

0.00122

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.0306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00560

AC:

381

AN:

68024

Other (OTH)

AF:

0.00568

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

120

160

200

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Feb 18, 2020

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Primary ciliary dyskinesia 3

Benign:1

Jun 15, 2021

Pars Genome Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.64

(source)

DANN

Benign

0.46

PhyloP100

-0.0030

La Branchor

0.54

BranchPoint Hunter

2.0

Mutation Taster

=100/0

polymorphism

(source)

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

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rs114717951

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over