rs10041113

Variant names:

• chr5-13844936-G-A
• rs10041113
• NM_001369.3:c.5172C>T

Your query was ambiguous. Multiple possible variants found:

• chr5-13844936-G-A
• chr5-13844936-G-C
• chr5-13844936-G-T

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.5172C>T​(p.Ala1724Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.363 in 1,613,462 control chromosomes in the GnomAD database, including 108,559 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.40 (12599 hom., cov: 32)
  • Exomes 𝑓: 0.36 (95960 hom.)
• Consequence: DNAH5 NM_001369.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:11
• Conservation: PhyloP100: -0.323
• Publications: 12 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=-0.55).
• BP6: Variant 5-13844936-G-A is Benign according to our data. Variant chr5-13844936-G-A is described in ClinVar as Benign. ClinVar VariationId is 178749.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.323 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.589 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH5	NM_001369.3	c.5172C>T	p.Ala1724Ala	synonymous_variant	Exon 32 of 79	ENST00000265104.5	NP_001360.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH5	ENST00000265104.5	c.5172C>T	p.Ala1724Ala	synonymous_variant	Exon 32 of 79	1	NM_001369.3	ENSP00000265104.4
DNAH5	ENST00000681290.1	c.5127C>T	p.Ala1709Ala	synonymous_variant	Exon 32 of 79			ENSP00000505288.1

Frequencies

GnomAD3 genomes AF: 0.401 AC: 60839 AN: 151816 Hom.: 12580 Cov.: 32

Gnomad AFR AF: 0.499

Gnomad AMI AF: 0.418

Gnomad AMR AF: 0.371

Gnomad ASJ AF: 0.347

Gnomad EAS AF: 0.607

Gnomad SAS AF: 0.346

Gnomad FIN AF: 0.316

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.352

Gnomad OTH AF: 0.400

GnomAD2 exomes AF: 0.379 AC: 95236 AN: 251394 AF XY: 0.372

Gnomad AFR exome AF: 0.502

Gnomad AMR exome AF: 0.362

Gnomad ASJ exome AF: 0.341

Gnomad EAS exome AF: 0.630

Gnomad FIN exome AF: 0.320

Gnomad NFE exome AF: 0.351

Gnomad OTH exome AF: 0.368

GnomAD4 exome AF: 0.359 AC: 524914 AN: 1461526 Hom.: 95960 Cov.: 40 AF XY: 0.358 AC XY: 259994 AN XY: 727102

African (AFR) AF: 0.497 AC: 16643 AN: 33466

American (AMR) AF: 0.368 AC: 16479 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.339 AC: 8858 AN: 26134

East Asian (EAS) AF: 0.559 AC: 22180 AN: 39698

South Asian (SAS) AF: 0.339 AC: 29210 AN: 86252

European-Finnish (FIN) AF: 0.326 AC: 17441 AN: 53420

Middle Eastern (MID) AF: 0.305 AC: 1758 AN: 5762

European-Non Finnish (NFE) AF: 0.351 AC: 389973 AN: 1111694

Other (OTH) AF: 0.371 AC: 22372 AN: 60378

GnomAD4 genome AF: 0.401 AC: 60900 AN: 151936 Hom.: 12599 Cov.: 32 AF XY: 0.398 AC XY: 29530 AN XY: 74266

African (AFR) AF: 0.499 AC: 20662 AN: 41408

American (AMR) AF: 0.371 AC: 5670 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.347 AC: 1204 AN: 3472

East Asian (EAS) AF: 0.606 AC: 3116 AN: 5138

South Asian (SAS) AF: 0.345 AC: 1667 AN: 4826

European-Finnish (FIN) AF: 0.316 AC: 3334 AN: 10550

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.352 AC: 23947 AN: 67968

Other (OTH) AF: 0.397 AC: 835 AN: 2102

Alfa AF: 0.371 Hom.: 8321

Bravo AF: 0.413

Asia WGS AF: 0.454 AC: 1578 AN: 3478

EpiCase AF: 0.349

EpiControl AF: 0.345

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:4

-

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

Significance: Benign

Review Status: no assertion criteria provided

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

Ala1724Ala in exon 32 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 50.0% (2201/4406) of African American chromosomes from a broad population by the NHLBI Exome Seque ncing Project (http://evs.gs.washington.edu/EVS; dbSNP rs10041113). -

-

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

- -

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 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. -

Sep 16, 2020

Natera, Inc.

Significance: Benign

Review Status: no assertion criteria provided

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

- -

Primary ciliary dyskinesia 3 Benign:2

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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	2.9
DANN	Benign	0.52
PhyloP100		-0.32
Mutation Taster		=96/4	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs10041113; hg19: chr5-13845045; COSMIC: COSV54225156;