5-13931096-G-C

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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 id is 163161.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-13931096-G-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.672 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH5	NM_001369.3	c.192+14C>G		intron_variant	Intron 2 of 78	ENST00000265104.5	NP_001360.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH5	ENST00000265104.5	c.192+14C>G		intron_variant	Intron 2 of 78	1	NM_001369.3	ENSP00000265104.4

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

GnomAD3 exomes AF: 0.371 AC: 93177 AN: 251132 Hom.: 19363 AF XY: 0.361 AC XY: 48959 AN XY: 135728

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 SAS exome AF: 0.359

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

Gnomad4 AFR exome AF: 0.622

Gnomad4 AMR exome AF: 0.425

Gnomad4 ASJ exome AF: 0.343

Gnomad4 EAS exome AF: 0.682

Gnomad4 SAS exome AF: 0.357

Gnomad4 FIN exome AF: 0.277

Gnomad4 NFE exome AF: 0.289

Gnomad4 OTH exome AF: 0.338

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

Gnomad4 AFR AF: 0.612

Gnomad4 AMR AF: 0.397

Gnomad4 ASJ AF: 0.350

Gnomad4 EAS AF: 0.691

Gnomad4 SAS AF: 0.374

Gnomad4 FIN AF: 0.284

Gnomad4 NFE AF: 0.298

Gnomad4 OTH AF: 0.408

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

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). -

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

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

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. -

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

- -

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.2
DANN	Benign	0.34

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

Other links and lift over

dbSNP: rs1530497; hg19: chr5-13931205; COSMIC: COSV54205634;