Genetic Variant DNAH5:c.3175-34G>A (chr5-13882849-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001369.3(DNAH5):c.3175-34G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.297 in 1,613,216 control chromosomes in the GnomAD database, including 73,953 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 6152 hom., cov: 32)

Exomes 𝑓: 0.30 ( 67801 hom. )

Consequence

DNAH5
NM_001369.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.197

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 links:

ENSG00000251423 (HGNC:40187):

ENSG00000251423 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 5-13882849-C-T is Benign according to our data. Variant chr5-13882849-C-T is described in ClinVar as [Benign]. Clinvar id is 258017.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.563 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH5	NM_001369.3 link	c.3175-34G>A		intron_variant	Intron 20 of 78	ENST00000265104.5	NP_001360.1	Q8TE73

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
DNAH5	ENST00000265104.5 link	c.3175-34G>A	intron_variant	Intron 20 of 78	1	NM_001369.3	ENSP00000265104.4	Q8TE73
DNAH5	ENST00000681290.1 link	c.3130-34G>A	intron_variant	Intron 20 of 78			ENSP00000505288.1	A0A7P0Z455
ENSG00000251423	ENST00000503244.2 link	n.254-13740C>T	intron_variant	Intron 1 of 2	4
ENSG00000251423	ENST00000637153.1 link	n.214-13740C>T	intron_variant	Intron 1 of 2	5

Frequencies

GnomAD3 genomes

AF:

0.276

AC:

41876

AN:

151870

Hom.:

6152

Cov.:

show subpopulations

Gnomad AFR

AF:

0.180

Gnomad AMI

AF:

0.370

Gnomad AMR

AF:

0.332

Gnomad ASJ

AF:

0.351

Gnomad EAS

AF:

0.581

Gnomad SAS

AF:

0.284

Gnomad FIN

AF:

0.270

Gnomad MID

AF:

0.304

Gnomad NFE

AF:

0.293

Gnomad OTH

AF:

0.297

GnomAD3 exomes

AF:

0.314

AC:

78936

AN:

251262

Hom.:

13446

AF XY:

0.313

AC XY:

42556

AN XY:

135802

show subpopulations

Gnomad AFR exome

AF:

0.174

Gnomad AMR exome

AF:

0.345

Gnomad ASJ exome

AF:

0.350

Gnomad EAS exome

AF:

0.597

Gnomad SAS exome

AF:

0.265

Gnomad FIN exome

AF:

0.274

Gnomad NFE exome

AF:

0.297

Gnomad OTH exome

AF:

0.323

GnomAD4 exome

AF:

0.299

AC:

437224

AN:

1461228

Hom.:

67801

Cov.:

AF XY:

0.299

AC XY:

217313

AN XY:

726982

show subpopulations

Gnomad4 AFR exome

AF:

0.167

Gnomad4 AMR exome

AF:

0.343

Gnomad4 ASJ exome

AF:

0.348

Gnomad4 EAS exome

AF:

0.584

Gnomad4 SAS exome

AF:

0.267

Gnomad4 FIN exome

AF:

0.279

Gnomad4 NFE exome

AF:

0.293

Gnomad4 OTH exome

AF:

0.306

GnomAD4 genome

AF:

0.276

AC:

41881

AN:

151988

Hom.:

6152

Cov.:

AF XY:

0.279

AC XY:

20745

AN XY:

74298

show subpopulations

Gnomad4 AFR

AF:

0.180

Gnomad4 AMR

AF:

0.332

Gnomad4 ASJ

AF:

0.351

Gnomad4 EAS

AF:

0.581

Gnomad4 SAS

AF:

0.283

Gnomad4 FIN

AF:

0.270

Gnomad4 NFE

AF:

0.293

Gnomad4 OTH

AF:

0.297

Alfa

AF:

0.284

Hom.:

3395

Bravo

AF:

0.280

Asia WGS

AF:

0.383

AC:

1332

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Primary ciliary dyskinesia 3

Benign:1

Jun 15, 2021

Pars Genome Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

2.1

DANN

Benign

0.61

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over