dbSNP rs4701995: DNAH5:c.3835-436C>T (chr5-13868428-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001369.3(DNAH5):c.3835-436C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.391 in 152,052 control chromosomes in the GnomAD database, including 12,023 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 ( 12023 hom., cov: 32)

Consequence

DNAH5
NM_001369.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.203

Publications

4 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.448 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH5	NM_001369.3 link	c.3835-436C>T		intron_variant	Intron 24 of 78	ENST00000265104.5	NP_001360.1	Q8TE73

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
DNAH5	ENST00000265104.5 link	c.3835-436C>T	intron_variant	Intron 24 of 78	1	NM_001369.3	ENSP00000265104.4	Q8TE73
DNAH5	ENST00000681290.1 link	c.3790-436C>T	intron_variant	Intron 24 of 78			ENSP00000505288.1	A0A7P0Z455
ENSG00000251423	ENST00000503244.2 link	n.253+7873G>A	intron_variant	Intron 1 of 2	4
ENSG00000251423	ENST00000637153.1 link	n.213+7913G>A	intron_variant	Intron 1 of 2	5

Frequencies

GnomAD3 genomes

AF:

0.391

AC:

59364

AN:

151934

Hom.:

12005

Cov.:

show subpopulations

Gnomad AFR

AF:

0.301

Gnomad AMI

AF:

0.325

Gnomad AMR

AF:

0.340

Gnomad ASJ

AF:

0.356

Gnomad EAS

AF:

0.260

Gnomad SAS

AF:

0.461

Gnomad FIN

AF:

0.487

Gnomad MID

AF:

0.332

Gnomad NFE

AF:

0.449

Gnomad OTH

AF:

0.397

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

GnomAD4 genome

AF:

0.391

AC:

59425

AN:

152052

Hom.:

12023

Cov.:

AF XY:

0.390

AC XY:

28962

AN XY:

74310

show subpopulations

African (AFR)

AF:

0.301

AC:

12475

AN:

41480

American (AMR)

AF:

0.340

AC:

5197

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.356

AC:

1234

AN:

3468

East Asian (EAS)

AF:

0.261

AC:

1351

AN:

5174

South Asian (SAS)

AF:

0.464

AC:

2233

AN:

4816

European-Finnish (FIN)

AF:

0.487

AC:

5147

AN:

10566

Middle Eastern (MID)

AF:

0.361

AC:

106

AN:

294

European-Non Finnish (NFE)

AF:

0.449

AC:

30544

AN:

67976

Other (OTH)

AF:

0.401

AC:

844

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1842

3684

5525

7367

9209

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

578

1156

1734

2312

2890

<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:

0.433

Hom.:

8260

Bravo

AF:

0.370

Asia WGS

AF:

0.382

AC:

1330

AN:

3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

4.3

(source)

DANN

Benign

0.71

PhyloP100

0.20

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over