5-13701427-T-C

Variant names:

Variant summary

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

The NM_001369.3(DNAH5):c.13348A>G(p.Ile4450Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.537 in 1,602,296 control chromosomes in the GnomAD database, including 233,685 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.53 ( 21311 hom., cov: 30)

Exomes 𝑓: 0.54 ( 212374 hom. )

Consequence

DNAH5
NM_001369.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:12

Conservation

PhyloP100: 0.805

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=5.3269225E-5).

BP6

Variant 5-13701427-T-C is Benign according to our data. Variant chr5-13701427-T-C is described in ClinVar as [Benign]. Clinvar id is 163132.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-13701427-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.542 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH5	NM_001369.3 link	c.13348A>G	p.Ile4450Val	missense_variant	Exon 77 of 79	ENST00000265104.5	NP_001360.1	Q8TE73

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DNAH5	ENST00000265104.5 link	c.13348A>G	p.Ile4450Val	missense_variant	Exon 77 of 79	1	NM_001369.3	ENSP00000265104.4	Q8TE73
DNAH5	ENST00000681290.1 link	c.13303A>G	p.Ile4435Val	missense_variant	Exon 77 of 79			ENSP00000505288.1	A0A7P0Z455
DNAH5	ENST00000683611.1 link	n.681A>G		non_coding_transcript_exon_variant	Exon 3 of 5

Frequencies

GnomAD3 genomes

AF:

0.529

AC:

80024

AN:

151236

Hom.:

21282

Cov.:

show subpopulations

Gnomad AFR

AF:

0.517

Gnomad AMI

AF:

0.589

Gnomad AMR

AF:

0.522

Gnomad ASJ

AF:

0.551

Gnomad EAS

AF:

0.442

Gnomad SAS

AF:

0.455

Gnomad FIN

AF:

0.532

Gnomad MID

AF:

0.561

Gnomad NFE

AF:

0.547

Gnomad OTH

AF:

0.536

GnomAD3 exomes

AF:

0.518

AC:

130100

AN:

250968

Hom.:

34086

AF XY:

0.516

AC XY:

70050

AN XY:

135796

show subpopulations

Gnomad AFR exome

AF:

0.518

Gnomad AMR exome

AF:

0.507

Gnomad ASJ exome

AF:

0.541

Gnomad EAS exome

AF:

0.422

Gnomad SAS exome

AF:

0.455

Gnomad FIN exome

AF:

0.530

Gnomad NFE exome

AF:

0.550

Gnomad OTH exome

AF:

0.531

GnomAD4 exome

AF:

0.538

AC:

780975

AN:

1450940

Hom.:

212374

Cov.:

AF XY:

0.535

AC XY:

386771

AN XY:

722426

show subpopulations

Gnomad4 AFR exome

AF:

0.506

Gnomad4 AMR exome

AF:

0.508

Gnomad4 ASJ exome

AF:

0.538

Gnomad4 EAS exome

AF:

0.406

Gnomad4 SAS exome

AF:

0.455

Gnomad4 FIN exome

AF:

0.529

Gnomad4 NFE exome

AF:

0.553

Gnomad4 OTH exome

AF:

0.530

GnomAD4 genome

AF:

0.529

AC:

80104

AN:

151356

Hom.:

21311

Cov.:

AF XY:

0.526

AC XY:

38835

AN XY:

73884

show subpopulations

Gnomad4 AFR

AF:

0.517

Gnomad4 AMR

AF:

0.522

Gnomad4 ASJ

AF:

0.551

Gnomad4 EAS

AF:

0.442

Gnomad4 SAS

AF:

0.455

Gnomad4 FIN

AF:

0.532

Gnomad4 NFE

AF:

0.547

Gnomad4 OTH

AF:

0.538

Alfa

AF:

0.543

Hom.:

54294

Bravo

AF:

0.530

TwinsUK

AF:

0.549

AC:

2034

ALSPAC

AF:

0.552

AC:

2127

ESP6500AA

AF:

0.505

AC:

2223

ESP6500EA

AF:

0.550

AC:

4726

ExAC

AF:

0.518

AC:

62936

Asia WGS

AF:

0.473

AC:

1648

AN:

3478

EpiCase

AF:

0.544

EpiControl

AF:

0.556

ClinVar

Significance: Benign

Submissions summary: Benign:12

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Feb 21, 2013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Ile4450Val in exon 77 of DNAH5: This variant is not expected to have clinical si gnificance because it has been identified in 49.5% (2183/4406) of African Americ an chromosomes from a broad population by the NHLBI Exome Sequencing Project (ht tp://evs.gs.washington.edu/EVS; dbSNP rs3734110). -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Primary ciliary dyskinesia

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Dec 11, 2014

Ambry Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Sep 16, 2020

Natera, Inc.

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Primary ciliary dyskinesia 3

Benign:3

Jun 15, 2021

Pars Genome Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 30, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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:2

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.059

BayesDel_addAF

Benign

-0.86

BayesDel_noAF

Benign

-0.87

CADD

Benign

9.5

DANN

Benign

0.95

DEOGEN2

Benign

0.037

Eigen

Benign

-0.55

Eigen_PC

Benign

-0.33

FATHMM_MKL

Benign

0.087

LIST_S2

Benign

0.45

MetaRNN

Benign

0.000053

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-0.17

PrimateAI

Benign

0.35

PROVEAN

Benign

0.67

REVEL

Benign

0.062

Sift

Benign

0.25

Polyphen

0.0

Vest4

0.019

MPC

0.078

ClinPred

0.0030

GERP RS

4.9

Varity_R

0.060

gMVP

0.35

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