5-13718913-T-G

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001369.3(DNAH5):c.12468A>C(p.Gly4156Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.413 in 1,612,042 control chromosomes in the GnomAD database, including 138,748 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.40 ( 12470 hom., cov: 32)

Exomes 𝑓: 0.41 ( 126278 hom. )

Consequence

DNAH5
NM_001369.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0460

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BP6

Variant 5-13718913-T-G is Benign according to our data. Variant chr5-13718913-T-G is described in ClinVar as [Benign]. Clinvar id is 178742.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-13718913-T-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.046 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.436 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH5	NM_001369.3 link	c.12468A>C	p.Gly4156Gly	synonymous_variant	Exon 72 of 79	ENST00000265104.5	NP_001360.1	Q8TE73

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH5	ENST00000265104.5 link	c.12468A>C	p.Gly4156Gly	synonymous_variant	Exon 72 of 79	1	NM_001369.3	ENSP00000265104.4		Q8TE73
DNAH5	ENST00000681290.1 link	c.12423A>C	p.Gly4141Gly	synonymous_variant	Exon 72 of 79			ENSP00000505288.1		A0A7P0Z455

Frequencies

GnomAD3 genomes

AF:

0.403

AC:

61243

AN:

151888

Hom.:

12452

Cov.:

show subpopulations

Gnomad AFR

AF:

0.396

Gnomad AMI

AF:

0.441

Gnomad AMR

AF:

0.414

Gnomad ASJ

AF:

0.414

Gnomad EAS

AF:

0.431

Gnomad SAS

AF:

0.452

Gnomad FIN

AF:

0.317

Gnomad MID

AF:

0.440

Gnomad NFE

AF:

0.412

Gnomad OTH

AF:

0.404

GnomAD3 exomes

AF:

0.414

AC:

103983

AN:

251176

Hom.:

21831

AF XY:

0.416

AC XY:

56484

AN XY:

135736

show subpopulations

Gnomad AFR exome

AF:

0.394

Gnomad AMR exome

AF:

0.442

Gnomad ASJ exome

AF:

0.418

Gnomad EAS exome

AF:

0.411

Gnomad SAS exome

AF:

0.453

Gnomad FIN exome

AF:

0.327

Gnomad NFE exome

AF:

0.415

Gnomad OTH exome

AF:

0.416

GnomAD4 exome

AF:

0.414

AC:

604683

AN:

1460036

Hom.:

126278

Cov.:

AF XY:

0.415

AC XY:

301515

AN XY:

726432

show subpopulations

Gnomad4 AFR exome

AF:

0.387

Gnomad4 AMR exome

AF:

0.436

Gnomad4 ASJ exome

AF:

0.408

Gnomad4 EAS exome

AF:

0.399

Gnomad4 SAS exome

AF:

0.454

Gnomad4 FIN exome

AF:

0.331

Gnomad4 NFE exome

AF:

0.415

Gnomad4 OTH exome

AF:

0.416

GnomAD4 genome

AF:

0.403

AC:

61311

AN:

152006

Hom.:

12470

Cov.:

AF XY:

0.398

AC XY:

29576

AN XY:

74286

show subpopulations

Gnomad4 AFR

AF:

0.396

Gnomad4 AMR

AF:

0.414

Gnomad4 ASJ

AF:

0.414

Gnomad4 EAS

AF:

0.431

Gnomad4 SAS

AF:

0.452

Gnomad4 FIN

AF:

0.317

Gnomad4 NFE

AF:

0.412

Gnomad4 OTH

AF:

0.407

Alfa

AF:

0.415

Hom.:

17047

Bravo

AF:

0.410

Asia WGS

AF:

0.447

AC:

1558

AN:

3478

EpiCase

AF:

0.421

EpiControl

AF:

0.433

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

Gly4156Gly in exon 72 of DNAH5: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue and is not located wi thin the splice consensus sequence. It has been identified in 42.4% (3649/8600) of European American chromosomes from a broad population by the NHLBI Exome Sequ encing Project (http://evs.gs.washington.edu/EVS; dbSNP rs30169). -

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

- -

Sep 16, 2020

Natera, Inc.

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Dec 10, 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. -

Primary ciliary dyskinesia 3

Benign:3

Jun 15, 2021

Pars Genome 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. -

Jul 30, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 10, 2018

GeneDx

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

-0.51

CADD

Benign

7.2

DANN

Benign

0.65

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