5-13718913-T-G

Variant names:

• chr5-13718913-T-G
• rs30169
• NM_001369.3:c.12468A>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

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 (★★). Synonymous variant affecting the same amino acid position (i.e. G4156G) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.40 (12470 hom., cov: 32)
  • Exomes 𝑓: 0.41 (126278 hom.)
• Consequence: DNAH5 NM_001369.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:12
• Conservation: PhyloP100: 0.0460
• Publications: 19 publications found

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 Gene-Disease associations (from GenCC):

• primary ciliary dyskinesia 3

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P, ClinGen
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 178742.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001369.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH5	NM_001369.3	MANE Select	c.12468A>C	p.Gly4156Gly	synonymous	Exon 72 of 79	NP_001360.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH5	ENST00000265104.5	TSL:1 MANE Select	c.12468A>C	p.Gly4156Gly	synonymous	Exon 72 of 79	ENSP00000265104.4
	DNAH5	ENST00000681290.1		c.12423A>C	p.Gly4141Gly	synonymous	Exon 72 of 79	ENSP00000505288.1

Frequencies

GnomAD3 genomes AF: 0.403 AC: 61243 AN: 151888 Hom.: 12452 Cov.: 32

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

GnomAD2 exomes AF: 0.414 AC: 103983 AN: 251176 AF XY: 0.416

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 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.: 41 AF XY: 0.415 AC XY: 301515 AN XY: 726432

African (AFR) AF: 0.387 AC: 12945 AN: 33436

American (AMR) AF: 0.436 AC: 19504 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.408 AC: 10666 AN: 26126

East Asian (EAS) AF: 0.399 AC: 15838 AN: 39688

South Asian (SAS) AF: 0.454 AC: 39109 AN: 86222

European-Finnish (FIN) AF: 0.331 AC: 17696 AN: 53412

Middle Eastern (MID) AF: 0.436 AC: 2514 AN: 5766

European-Non Finnish (NFE) AF: 0.415 AC: 461313 AN: 1110336

Other (OTH) AF: 0.416 AC: 25098 AN: 60336

GnomAD4 genome AF: 0.403 AC: 61311 AN: 152006 Hom.: 12470 Cov.: 32 AF XY: 0.398 AC XY: 29576 AN XY: 74286

African (AFR) AF: 0.396 AC: 16425 AN: 41466

American (AMR) AF: 0.414 AC: 6321 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.414 AC: 1439 AN: 3472

East Asian (EAS) AF: 0.431 AC: 2230 AN: 5170

South Asian (SAS) AF: 0.452 AC: 2168 AN: 4800

European-Finnish (FIN) AF: 0.317 AC: 3342 AN: 10548

Middle Eastern (MID) AF: 0.435 AC: 128 AN: 294

European-Non Finnish (NFE) AF: 0.412 AC: 27996 AN: 67970

Other (OTH) AF: 0.407 AC: 860 AN: 2112

Alfa AF: 0.415 Hom.: 21076

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

Submissions by phenotype

not specified Benign:4

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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).

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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

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

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

Jun 15, 2021

Pars Genome 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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	7.2
DANN	Benign	0.65
PhyloP100		0.046
Mutation Taster		=79/21	polymorphism (auto)

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

Other links and lift over

dbSNP: rs30169; hg19: chr5-13719022; COSMIC: COSV54212375;