dbSNP rs7704417: DNAH5:c.4796+41G>A (chr5-13862507-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.4796+41G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.403 in 1,573,626 control chromosomes in the GnomAD database, including 129,624 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.39 ( 11963 hom., cov: 31)

Exomes 𝑓: 0.40 ( 117661 hom. )

Consequence

DNAH5
NM_001369.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.79

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=-0.95).

BP6

Variant 5-13862507-C-T is Benign according to our data. Variant chr5-13862507-C-T is described in ClinVar as [Benign]. Clinvar id is 258035.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.451 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH5	NM_001369.3 link	c.4796+41G>A		intron_variant	Intron 29 of 78	ENST00000265104.5	NP_001360.1	Q8TE73

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
DNAH5	ENST00000265104.5 link	c.4796+41G>A	intron_variant	Intron 29 of 78	1	NM_001369.3	ENSP00000265104.4	Q8TE73
DNAH5	ENST00000681290.1 link	c.4751+41G>A	intron_variant	Intron 29 of 78			ENSP00000505288.1	A0A7P0Z455
ENSG00000251423	ENST00000503244.2 link	n.253+1952C>T	intron_variant	Intron 1 of 2	4
ENSG00000251423	ENST00000637153.1 link	n.213+1992C>T	intron_variant	Intron 1 of 2	5

Frequencies

GnomAD3 genomes

AF:

0.394

AC:

59820

AN:

151720

Hom.:

11947

Cov.:

show subpopulations

Gnomad AFR

AF:

0.386

Gnomad AMI

AF:

0.312

Gnomad AMR

AF:

0.330

Gnomad ASJ

AF:

0.317

Gnomad EAS

AF:

0.260

Gnomad SAS

AF:

0.465

Gnomad FIN

AF:

0.463

Gnomad MID

AF:

0.322

Gnomad NFE

AF:

0.414

Gnomad OTH

AF:

0.390

GnomAD3 exomes

AF:

0.385

AC:

96122

AN:

249376

Hom.:

19339

AF XY:

0.392

AC XY:

52886

AN XY:

134866

show subpopulations

Gnomad AFR exome

AF:

0.381

Gnomad AMR exome

AF:

0.282

Gnomad ASJ exome

AF:

0.325

Gnomad EAS exome

AF:

0.237

Gnomad SAS exome

AF:

0.477

Gnomad FIN exome

AF:

0.455

Gnomad NFE exome

AF:

0.410

Gnomad OTH exome

AF:

0.369

GnomAD4 exome

AF:

0.404

AC:

573751

AN:

1421790

Hom.:

117661

Cov.:

AF XY:

0.405

AC XY:

287719

AN XY:

709762

show subpopulations

Gnomad4 AFR exome

AF:

0.392

Gnomad4 AMR exome

AF:

0.290

Gnomad4 ASJ exome

AF:

0.325

Gnomad4 EAS exome

AF:

0.258

Gnomad4 SAS exome

AF:

0.472

Gnomad4 FIN exome

AF:

0.454

Gnomad4 NFE exome

AF:

0.409

Gnomad4 OTH exome

AF:

0.391

GnomAD4 genome

AF:

0.394

AC:

59888

AN:

151836

Hom.:

11963

Cov.:

AF XY:

0.393

AC XY:

29167

AN XY:

74232

show subpopulations

Gnomad4 AFR

AF:

0.386

Gnomad4 AMR

AF:

0.330

Gnomad4 ASJ

AF:

0.317

Gnomad4 EAS

AF:

0.261

Gnomad4 SAS

AF:

0.467

Gnomad4 FIN

AF:

0.463

Gnomad4 NFE

AF:

0.414

Gnomad4 OTH

AF:

0.394

Alfa

AF:

0.395

Hom.:

20134

Bravo

AF:

0.379

Asia WGS

AF:

0.388

AC:

1350

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

-0.95

CADD

Benign

0.020

DANN

Benign

0.60

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