5-13931231-C-T

Position:

chr5-13931231-C-T

Variant summary

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

The NM_001369.3(DNAH5):c.71G>A(p.Gly24Glu) variant causes a missense change. The variant allele was found at a frequency of 0.324 in 1,613,668 control chromosomes in the GnomAD database, including 92,045 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.40 ( 13455 hom., cov: 33)

Exomes 𝑓: 0.32 ( 78590 hom. )

Consequence

DNAH5
NM_001369.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: 5.59

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:

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 (MetaRNN=4.3286577E-6).

BP6

Variant 5-13931231-C-T is Benign according to our data. Variant chr5-13931231-C-T is described in ClinVar as [Benign]. Clinvar id is 163159.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-13931231-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.679 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH5	NM_001369.3 linkuse as main transcript	c.71G>A	p.Gly24Glu	missense_variant	2/79	ENST00000265104.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH5	ENST00000265104.5 linkuse as main transcript	c.71G>A	p.Gly24Glu	missense_variant	2/79	1	NM_001369.3	P4

Frequencies

GnomAD3 genomes

AF:

0.399

AC:

60659

AN:

151986

Hom.:

13436

Cov.:

show subpopulations

Gnomad AFR

AF:

0.571

Gnomad AMI

AF:

0.274

Gnomad AMR

AF:

0.392

Gnomad ASJ

AF:

0.346

Gnomad EAS

AF:

0.698

Gnomad SAS

AF:

0.375

Gnomad FIN

AF:

0.284

Gnomad MID

AF:

0.354

Gnomad NFE

AF:

0.297

Gnomad OTH

AF:

0.396

GnomAD3 exomes

AF:

0.367

AC:

92279

AN:

251192

Hom.:

18898

AF XY:

0.358

AC XY:

48582

AN XY:

135742

show subpopulations

Gnomad AFR exome

AF:

0.576

Gnomad AMR exome

AF:

0.421

Gnomad ASJ exome

AF:

0.332

Gnomad EAS exome

AF:

0.695

Gnomad SAS exome

AF:

0.360

Gnomad FIN exome

AF:

0.271

Gnomad NFE exome

AF:

0.293

Gnomad OTH exome

AF:

0.336

GnomAD4 exome

AF:

0.316

AC:

462539

AN:

1461564

Hom.:

78590

Cov.:

AF XY:

0.316

AC XY:

229815

AN XY:

727088

show subpopulations

Gnomad4 AFR exome

AF:

0.580

Gnomad4 AMR exome

AF:

0.423

Gnomad4 ASJ exome

AF:

0.337

Gnomad4 EAS exome

AF:

0.694

Gnomad4 SAS exome

AF:

0.357

Gnomad4 FIN exome

AF:

0.276

Gnomad4 NFE exome

AF:

0.288

Gnomad4 OTH exome

AF:

0.334

GnomAD4 genome

AF:

0.399

AC:

60722

AN:

152104

Hom.:

13455

Cov.:

AF XY:

0.398

AC XY:

29605

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.571

Gnomad4 AMR

AF:

0.393

Gnomad4 ASJ

AF:

0.346

Gnomad4 EAS

AF:

0.698

Gnomad4 SAS

AF:

0.374

Gnomad4 FIN

AF:

0.284

Gnomad4 NFE

AF:

0.297

Gnomad4 OTH

AF:

0.395

Alfa

AF:

0.318

Hom.:

19761

Bravo

AF:

0.415

TwinsUK

AF:

0.285

AC:

1056

ALSPAC

AF:

0.282

AC:

1085

ESP6500AA

AF:

0.563

AC:

2480

ESP6500EA

AF:

0.302

AC:

2599

ExAC

AF:

0.369

AC:

44816

Asia WGS

AF:

0.508

AC:

1764

AN:

3476

EpiCase

AF:

0.283

EpiControl

AF:

0.287

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Feb 21, 2013	Gly24Glu in exon 2 of DNAH5: This variant is not expected to have clinical signi ficance because it has been identified in 43.7% (1926/4406) of African American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http: //evs.gs.washington.edu/EVS; dbSNP rs1530496). -

Primary ciliary dyskinesia

Benign:3

Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Sep 16, 2020	- -
Benign, criteria provided, single submitter	clinical testing	Ambry Genetics	Dec 01, 2014	This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -

Primary ciliary dyskinesia 3

Benign:3

Benign, criteria provided, single submitter	clinical testing	Pars Genome Lab	Jun 15, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 30, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.056

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.70

CADD

Benign

DANN

Benign

0.50

DEOGEN2

Benign

0.019

Eigen

Benign

-0.81

Eigen_PC

Benign

-0.45

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.33

MetaRNN

Benign

0.0000043

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-3.0

MutationTaster

Benign

1.0

PrimateAI

Benign

0.47

PROVEAN

Benign

4.0

REVEL

Benign

0.15

Sift

Benign

1.0

Polyphen

0.0

Vest4

0.037

MPC

0.12

ClinPred

0.0094

GERP RS

5.6

Varity_R

0.14

gMVP

0.33

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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