Genetic Variant DNAH5:c.5115-49G>C (chr5-13845042-C-G) – 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.5115-49G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.362 in 1,580,278 control chromosomes in the GnomAD database, including 105,419 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.40 ( 12616 hom., cov: 32)

Exomes 𝑓: 0.36 ( 92803 hom. )

Consequence

DNAH5
NM_001369.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.231

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 5-13845042-C-G is Benign according to our data. Variant chr5-13845042-C-G is described in ClinVar as [Benign]. Clinvar id is 258041.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.59 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH5	NM_001369.3 link	c.5115-49G>C		intron_variant	Intron 31 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.5115-49G>C		intron_variant	Intron 31 of 78	1	NM_001369.3	ENSP00000265104.4		Q8TE73
DNAH5	ENST00000681290.1 link	c.5070-49G>C		intron_variant	Intron 31 of 78			ENSP00000505288.1		A0A7P0Z455

Frequencies

GnomAD3 genomes

AF:

0.401

AC:

60871

AN:

151728

Hom.:

12597

Cov.:

show subpopulations

Gnomad AFR

AF:

0.499

Gnomad AMI

AF:

0.418

Gnomad AMR

AF:

0.371

Gnomad ASJ

AF:

0.347

Gnomad EAS

AF:

0.608

Gnomad SAS

AF:

0.349

Gnomad FIN

AF:

0.316

Gnomad MID

AF:

0.282

Gnomad NFE

AF:

0.353

Gnomad OTH

AF:

0.399

GnomAD3 exomes

AF:

0.376

AC:

89974

AN:

239400

Hom.:

17488

AF XY:

0.370

AC XY:

48186

AN XY:

130360

show subpopulations

Gnomad AFR exome

AF:

0.498

Gnomad AMR exome

AF:

0.359

Gnomad ASJ exome

AF:

0.340

Gnomad EAS exome

AF:

0.629

Gnomad SAS exome

AF:

0.338

Gnomad FIN exome

AF:

0.319

Gnomad NFE exome

AF:

0.348

Gnomad OTH exome

AF:

0.367

GnomAD4 exome

AF:

0.357

AC:

510369

AN:

1428432

Hom.:

92803

Cov.:

AF XY:

0.356

AC XY:

253454

AN XY:

712376

show subpopulations

Gnomad4 AFR exome

AF:

0.495

Gnomad4 AMR exome

AF:

0.366

Gnomad4 ASJ exome

AF:

0.338

Gnomad4 EAS exome

AF:

0.559

Gnomad4 SAS exome

AF:

0.337

Gnomad4 FIN exome

AF:

0.326

Gnomad4 NFE exome

AF:

0.349

Gnomad4 OTH exome

AF:

0.368

GnomAD4 genome

AF:

0.401

AC:

60932

AN:

151846

Hom.:

12616

Cov.:

AF XY:

0.398

AC XY:

29550

AN XY:

74210

show subpopulations

Gnomad4 AFR

AF:

0.499

Gnomad4 AMR

AF:

0.371

Gnomad4 ASJ

AF:

0.347

Gnomad4 EAS

AF:

0.608

Gnomad4 SAS

AF:

0.348

Gnomad4 FIN

AF:

0.316

Gnomad4 NFE

AF:

0.353

Gnomad4 OTH

AF:

0.397

Alfa

AF:

0.295

Hom.:

1139

Bravo

AF:

0.413

Asia WGS

AF:

0.454

AC:

1576

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 11, 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

-0.86

CADD

Benign

5.3

DANN

Benign

0.30

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

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