5-13931096-G-C

Variant names:

• chr5-13931096-G-C
• rs1530497
• NM_001369.3:c.192+14C>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001369.3(DNAH5):​c.192+14C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.327 in 1,613,588 control chromosomes in the GnomAD database, including 94,100 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.41 (14517 hom., cov: 32)
  • Exomes 𝑓: 0.32 (79583 hom.)
• Consequence: DNAH5 NM_001369.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: -0.104
• Publications: 6 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 5-13931096-G-C is Benign according to our data. Variant chr5-13931096-G-C is described in ClinVar as Benign. ClinVar VariationId is 163161.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.672 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.192+14C>G		intron	N/A	NP_001360.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH5	ENST00000265104.5	TSL:1 MANE Select	c.192+14C>G		intron	N/A	ENSP00000265104.4
	DNAH5	ENST00000681290.1		c.147+14C>G		intron	N/A	ENSP00000505288.1
	DNAH5	ENST00000508040.1	TSL:2	n.551+14C>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.411 AC: 62445 AN: 151946 Hom.: 14494 Cov.: 32

Gnomad AFR AF: 0.612

Gnomad AMI AF: 0.273

Gnomad AMR AF: 0.396

Gnomad ASJ AF: 0.350

Gnomad EAS AF: 0.691

Gnomad SAS AF: 0.375

Gnomad FIN AF: 0.284

Gnomad MID AF: 0.360

Gnomad NFE AF: 0.298

Gnomad OTH AF: 0.409

GnomAD2 exomes AF: 0.371 AC: 93177 AN: 251132 AF XY: 0.361

Gnomad AFR exome AF: 0.618

Gnomad AMR exome AF: 0.424

Gnomad ASJ exome AF: 0.339

Gnomad EAS exome AF: 0.692

Gnomad FIN exome AF: 0.271

Gnomad NFE exome AF: 0.294

Gnomad OTH exome AF: 0.338

GnomAD4 exome AF: 0.318 AC: 464938 AN: 1461524 Hom.: 79583 Cov.: 39 AF XY: 0.318 AC XY: 230910 AN XY: 727104

African (AFR) AF: 0.622 AC: 20805 AN: 33462

American (AMR) AF: 0.425 AC: 19009 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.343 AC: 8961 AN: 26126

East Asian (EAS) AF: 0.682 AC: 27073 AN: 39674

South Asian (SAS) AF: 0.357 AC: 30799 AN: 86250

European-Finnish (FIN) AF: 0.277 AC: 14783 AN: 53416

Middle Eastern (MID) AF: 0.326 AC: 1879 AN: 5766

European-Non Finnish (NFE) AF: 0.289 AC: 321236 AN: 1111736

Other (OTH) AF: 0.338 AC: 20393 AN: 60378

GnomAD4 genome AF: 0.411 AC: 62520 AN: 152064 Hom.: 14517 Cov.: 32 AF XY: 0.410 AC XY: 30457 AN XY: 74354

African (AFR) AF: 0.612 AC: 25369 AN: 41456

American (AMR) AF: 0.397 AC: 6053 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.350 AC: 1213 AN: 3468

East Asian (EAS) AF: 0.691 AC: 3572 AN: 5168

South Asian (SAS) AF: 0.374 AC: 1800 AN: 4810

European-Finnish (FIN) AF: 0.284 AC: 3011 AN: 10584

Middle Eastern (MID) AF: 0.366 AC: 107 AN: 292

European-Non Finnish (NFE) AF: 0.298 AC: 20285 AN: 67998

Other (OTH) AF: 0.408 AC: 861 AN: 2110

Alfa AF: 0.338 Hom.: 1738

Bravo AF: 0.428

Asia WGS AF: 0.511 AC: 1774 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:4

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

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

Feb 21, 2013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

192+14C>G in intron 2 of DNAH5: This variant is not expected to have clinical si gnificance because it is not located within the conserved splice consensus seque nce. It has been identified in 39.4% (1738/4406) of African American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.wa shington.edu/EVS; dbSNP rs1530497).

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 3 Benign:3

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.

Jun 15, 2021

Pars Genome Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

Primary ciliary dyskinesia Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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	-0.88
CADD	Benign	3.2
DANN	Benign	0.34
PhyloP100		-0.10
Mutation Taster		=100/0	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: rs1530497; hg19: chr5-13931205;