rs199959119

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.2578-36A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000727 in 1,530,352 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00087 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00071 ( 3 hom. )

Consequence

DNAH5
NM_001369.3 intron

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.05

Publications

0 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

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 5-13886165-T-A is Benign according to our data. Variant chr5-13886165-T-A is described in ClinVar as Likely_benign. ClinVar VariationId is 258013.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population mid. GnomAdExome4 allele frequency = 0.000711 (985/1384790) while in subpopulation MID AF = 0.0107 (55/5160). AF 95% confidence interval is 0.00841. There are 3 homozygotes in GnomAdExome4. There are 515 alleles in the male GnomAdExome4 subpopulation. Median coverage is 29. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 3 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH5	NM_001369.3 link	c.2578-36A>T		intron_variant	Intron 17 of 78	ENST00000265104.5	NP_001360.1	Q8TE73

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
DNAH5	ENST00000265104.5 link	c.2578-36A>T	intron_variant	Intron 17 of 78	1	NM_001369.3	ENSP00000265104.4	Q8TE73
DNAH5	ENST00000681290.1 link	c.2533-36A>T	intron_variant	Intron 17 of 78			ENSP00000505288.1	A0A7P0Z455
ENSG00000251423	ENST00000503244.2 link	n.254-10424T>A	intron_variant	Intron 1 of 2	4
ENSG00000251423	ENST00000637153.1 link	n.214-10424T>A	intron_variant	Intron 1 of 2	5

Frequencies

GnomAD3 genomes

AF:

0.000879

AC:

128

AN:

145546

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000177

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00164

Gnomad ASJ

AF:

0.000873

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000642

Gnomad FIN

AF:

0.000244

Gnomad MID

AF:

0.0164

Gnomad NFE

AF:

0.00117

Gnomad OTH

AF:

0.00297

GnomAD2 exomes

AF:

0.000875

AC:

157

AN:

179332

AF XY:

0.000925

show subpopulations

Gnomad AFR exome

AF:

0.000170

Gnomad AMR exome

AF:

0.000922

Gnomad ASJ exome

AF:

0.000792

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000457

Gnomad NFE exome

AF:

0.00135

Gnomad OTH exome

AF:

0.00165

GnomAD4 exome

AF:

0.000711

AC:

985

AN:

1384790

Hom.:

Cov.:

AF XY:

0.000749

AC XY:

515

AN XY:

687884

show subpopulations

African (AFR)

AF:

0.000288

AC:

AN:

31296

American (AMR)

AF:

0.000680

AC:

AN:

38220

Ashkenazi Jewish (ASJ)

AF:

0.000793

AC:

AN:

25212

East Asian (EAS)

AF:

0.00

AC:

AN:

37648

South Asian (SAS)

AF:

0.000493

AC:

AN:

81128

European-Finnish (FIN)

AF:

0.000202

AC:

AN:

39668

Middle Eastern (MID)

AF:

0.0107

AC:

AN:

5160

European-Non Finnish (NFE)

AF:

0.000715

AC:

764

AN:

1068790

Other (OTH)

AF:

0.00109

AC:

AN:

57668

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

106

158

211

264

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

110

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000872

AC:

127

AN:

145562

Hom.:

Cov.:

AF XY:

0.000880

AC XY:

AN XY:

70482

show subpopulations

African (AFR)

AF:

0.000176

AC:

AN:

39676

American (AMR)

AF:

0.00164

AC:

AN:

14648

Ashkenazi Jewish (ASJ)

AF:

0.000873

AC:

AN:

3438

East Asian (EAS)

AF:

0.00

AC:

AN:

4974

South Asian (SAS)

AF:

0.000646

AC:

AN:

4646

European-Finnish (FIN)

AF:

0.000244

AC:

AN:

8212

Middle Eastern (MID)

AF:

0.0144

AC:

AN:

278

European-Non Finnish (NFE)

AF:

0.00117

AC:

AN:

66756

Other (OTH)

AF:

0.00296

AC:

AN:

2030

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00116

Hom.:

Bravo

AF:

0.000910

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

1.8

(source)

DANN

Benign

0.64

PhyloP100

1.1

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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