Genetic Variant DNAH5:c.5272-21_5272-15dupTTTTTTT (chr5-13841918-C-CAAAAAAA) – 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.5272-21_5272-15dupTTTTTTT variant causes a 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 0.00023 ( 0 hom., cov: 0)

Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

DNAH5
NM_001369.3 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.617

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:

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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.5272-21_5272-15dupTTTTTTT		intron_variant	Intron 32 of 78	ENST00000265104.5	NP_001360.1	Q8TE73

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH5	ENST00000265104.5 link	c.5272-15_5272-14insTTTTTTT		intron_variant	Intron 32 of 78	1	NM_001369.3	ENSP00000265104.4		Q8TE73
DNAH5	ENST00000681290.1 link	c.5227-15_5227-14insTTTTTTT		intron_variant	Intron 32 of 78			ENSP00000505288.1		A0A7P0Z455

Frequencies

GnomAD3 genomes

AF:

0.000229

AC:

AN:

104626

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000142

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000460

Gnomad ASJ

AF:

0.000337

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000529

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000256

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000107

AC:

AN:

488002

Hom.:

Cov.:

AF XY:

0.000110

AC XY:

AN XY:

263782

show subpopulations

African (AFR)

AF:

0.000398

AC:

AN:

12568

American (AMR)

AF:

0.000261

AC:

AN:

19186

Ashkenazi Jewish (ASJ)

AF:

0.0000721

AC:

AN:

13878

East Asian (EAS)

AF:

0.0000737

AC:

AN:

27146

South Asian (SAS)

AF:

0.000178

AC:

AN:

45024

European-Finnish (FIN)

AF:

0.0000373

AC:

AN:

26782

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1990

European-Non Finnish (NFE)

AF:

0.0000949

AC:

AN:

316054

Other (OTH)

AF:

0.00

AC:

AN:

25374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.436

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.000229

AC:

AN:

104626

Hom.:

Cov.:

AF XY:

0.000254

AC XY:

AN XY:

47228

show subpopulations

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

African (AFR)

AF:

0.000142

AC:

AN:

28130

American (AMR)

AF:

0.000460

AC:

AN:

8698

Ashkenazi Jewish (ASJ)

AF:

0.000337

AC:

AN:

2964

East Asian (EAS)

AF:

0.00

AC:

AN:

3136

South Asian (SAS)

AF:

0.00

AC:

AN:

2698

European-Finnish (FIN)

AF:

0.000529

AC:

AN:

1892

Middle Eastern (MID)

AF:

0.00

AC:

AN:

158

European-Non Finnish (NFE)

AF:

0.000256

AC:

AN:

54794

Other (OTH)

AF:

0.00

AC:

AN:

1390

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000351372), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.387

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

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.62

Splicing

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

Publications

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5-13841918-CAAAAAAAAAAA-CAAAAAAAAAAAAAAAAAA

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