Genetic Variant DNAH5:c.2578-8_2578-7dupTT (chr5-13886135-C-CAA) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001369.3(DNAH5):c.2578-8_2578-7dupTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00062 ( 0 hom., cov: 0)

Exomes 𝑓: 0.0013 ( 1 hom. )

Consequence

DNAH5
NM_001369.3 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0110

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: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH5	NM_001369.3 link	c.2578-8_2578-7dupTT		splice_region_variant, intron_variant	Intron 17 of 78	ENST00000265104.5	NP_001360.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
DNAH5	ENST00000265104.5 link	c.2578-7_2578-6insTT	splice_region_variant, intron_variant	Intron 17 of 78	1	NM_001369.3	ENSP00000265104.4
DNAH5	ENST00000681290.1 link	c.2533-7_2533-6insTT	splice_region_variant, intron_variant	Intron 17 of 78			ENSP00000505288.1
ENSG00000251423	ENST00000503244.2 link	n.254-10454_254-10453insAA	intron_variant	Intron 1 of 2	4
ENSG00000251423	ENST00000637153.1 link	n.214-10454_214-10453insAA	intron_variant	Intron 1 of 2	5

Frequencies

GnomAD3 genomes

AF:

0.000622

AC:

AN:

123876

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00207

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000332

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000340

Gnomad OTH

AF:

0.000604

GnomAD4 exome

AF:

0.00127

AC:

1544

AN:

1215358

Hom.:

Cov.:

AF XY:

0.00127

AC XY:

766

AN XY:

600898

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00466

AC:

124

AN:

26626

American (AMR)

AF:

0.00315

AC:

AN:

27280

Ashkenazi Jewish (ASJ)

AF:

0.00159

AC:

AN:

20796

East Asian (EAS)

AF:

0.00303

AC:

AN:

32692

South Asian (SAS)

AF:

0.00317

AC:

207

AN:

65254

European-Finnish (FIN)

AF:

0.00153

AC:

AN:

31290

Middle Eastern (MID)

AF:

0.00170

AC:

AN:

3530

European-Non Finnish (NFE)

AF:

0.000897

AC:

859

AN:

957154

Other (OTH)

AF:

0.00162

AC:

AN:

50736

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.273

Heterozygous variant carriers

158

315

473

630

788

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

104

130

<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:

0.000622

AC:

AN:

123854

Hom.:

Cov.:

AF XY:

0.000545

AC XY:

AN XY:

58710

show subpopulations

African (AFR)

AF:

0.00207

AC:

AN:

33800

American (AMR)

AF:

0.000332

AC:

AN:

12048

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3012

East Asian (EAS)

AF:

0.00

AC:

AN:

3582

South Asian (SAS)

AF:

0.00

AC:

AN:

3852

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5988

Middle Eastern (MID)

AF:

0.00

AC:

AN:

236

European-Non Finnish (NFE)

AF:

0.0000340

AC:

AN:

58862

Other (OTH)

AF:

0.000602

AC:

AN:

1662

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

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:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.011

Splicing

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

Publications

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5-13886135-CAAAAAAAAAA-CAAAAAAAAAAAA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over