Genetic Variant DNAH5:c.12+24654T>C (chr5-13986994-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is . The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000681290.1(DNAH5):c.12+24654T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.39 in 151,960 control chromosomes in the GnomAD database, including 11,877 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.39 ( 11877 hom., cov: 31)

Consequence

DNAH5
ENST00000681290.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.78

Publications

5 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:

ENSG00000307550 (HGNC:59003):

ENSG00000307550 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript ENST00000681290.1, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.07).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.662 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000681290.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH5	ENST00000681290.1		c.12+24654T>C		intron	N/A	ENSP00000505288.1	A0A7P0Z455
	ENSG00000307550	ENST00000827039.1		n.338A>G		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes

AF:

0.390

AC:

59200

AN:

151842

Hom.:

11862

Cov.:

show subpopulations

Gnomad AFR

AF:

0.437

Gnomad AMI

AF:

0.364

Gnomad AMR

AF:

0.382

Gnomad ASJ

AF:

0.337

Gnomad EAS

AF:

0.681

Gnomad SAS

AF:

0.324

Gnomad FIN

AF:

0.346

Gnomad MID

AF:

0.402

Gnomad NFE

AF:

0.356

Gnomad OTH

AF:

0.377

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.390

AC:

59262

AN:

151960

Hom.:

11877

Cov.:

AF XY:

0.390

AC XY:

28963

AN XY:

74274

show subpopulations

African (AFR)

AF:

0.437

AC:

18111

AN:

41418

American (AMR)

AF:

0.382

AC:

5839

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.337

AC:

1168

AN:

3470

East Asian (EAS)

AF:

0.681

AC:

3505

AN:

5146

South Asian (SAS)

AF:

0.322

AC:

1553

AN:

4816

European-Finnish (FIN)

AF:

0.346

AC:

3655

AN:

10550

Middle Eastern (MID)

AF:

0.405

AC:

119

AN:

294

European-Non Finnish (NFE)

AF:

0.356

AC:

24184

AN:

67976

Other (OTH)

AF:

0.379

AC:

797

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1866

3733

5599

7466

9332

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

564

1128

1692

2256

2820

<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:

0.357

Hom.:

17109

Bravo

AF:

0.395

Asia WGS

AF:

0.509

AC:

1770

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.1

CADD

Benign

0.19

(source)

DANN

Benign

0.22

PhyloP100

-1.8

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over