rs1348691

Variant names:

• chr5-13829499-G-A
• rs1348691
• NM_001369.3:c.6444+11C>T

Your query was ambiguous. Multiple possible variants found:

• chr5-13829499-G-A
• chr5-13829499-G-T

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.6444+11C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.373 in 1,612,558 control chromosomes in the GnomAD database, including 114,252 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.40 (12277 hom., cov: 32)
  • Exomes 𝑓: 0.37 (101975 hom.)
• Consequence: DNAH5 NM_001369.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: 1.07
• Publications: 5 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=-0.82).
• BP6: Variant 5-13829499-G-A is Benign according to our data. Variant chr5-13829499-G-A is described in ClinVar as Benign. ClinVar VariationId is 163144.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.592 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH5	NM_001369.3	c.6444+11C>T		intron_variant	Intron 38 of 78	ENST00000265104.5	NP_001360.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH5	ENST00000265104.5	c.6444+11C>T		intron_variant	Intron 38 of 78	1	NM_001369.3	ENSP00000265104.4
DNAH5	ENST00000681290.1	c.6399+11C>T		intron_variant	Intron 38 of 78			ENSP00000505288.1
DNAH5	ENST00000683090.1	n.1375+11C>T		intron_variant	Intron 3 of 6

Frequencies

GnomAD3 genomes AF: 0.398 AC: 60510 AN: 151878 Hom.: 12261 Cov.: 32

Gnomad AFR AF: 0.461

Gnomad AMI AF: 0.454

Gnomad AMR AF: 0.383

Gnomad ASJ AF: 0.366

Gnomad EAS AF: 0.610

Gnomad SAS AF: 0.333

Gnomad FIN AF: 0.318

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.366

Gnomad OTH AF: 0.399

GnomAD2 exomes AF: 0.384 AC: 96539 AN: 251110 AF XY: 0.379

Gnomad AFR exome AF: 0.464

Gnomad AMR exome AF: 0.373

Gnomad ASJ exome AF: 0.362

Gnomad EAS exome AF: 0.624

Gnomad FIN exome AF: 0.325

Gnomad NFE exome AF: 0.366

Gnomad OTH exome AF: 0.381

GnomAD4 exome AF: 0.371 AC: 541690 AN: 1460562 Hom.: 101975 Cov.: 34 AF XY: 0.369 AC XY: 267884 AN XY: 726674

African (AFR) AF: 0.459 AC: 15356 AN: 33438

American (AMR) AF: 0.377 AC: 16877 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.359 AC: 9388 AN: 26124

East Asian (EAS) AF: 0.562 AC: 22319 AN: 39688

South Asian (SAS) AF: 0.330 AC: 28440 AN: 86236

European-Finnish (FIN) AF: 0.328 AC: 17497 AN: 53418

Middle Eastern (MID) AF: 0.336 AC: 1914 AN: 5698

European-Non Finnish (NFE) AF: 0.366 AC: 406993 AN: 1110918

Other (OTH) AF: 0.380 AC: 22906 AN: 60334

GnomAD4 genome AF: 0.398 AC: 60563 AN: 151996 Hom.: 12277 Cov.: 32 AF XY: 0.396 AC XY: 29395 AN XY: 74288

African (AFR) AF: 0.461 AC: 19103 AN: 41420

American (AMR) AF: 0.383 AC: 5854 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.366 AC: 1267 AN: 3464

East Asian (EAS) AF: 0.609 AC: 3148 AN: 5166

South Asian (SAS) AF: 0.332 AC: 1596 AN: 4812

European-Finnish (FIN) AF: 0.318 AC: 3364 AN: 10566

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.366 AC: 24885 AN: 67984

Other (OTH) AF: 0.397 AC: 837 AN: 2110

Alfa AF: 0.384 Hom.: 2483

Bravo AF: 0.411

Asia WGS AF: 0.454 AC: 1579 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:9

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

6444+11C>T in intron 38 of DNAH5: This variant is not expected to have clinical significance because it is not located within the conserved splice consensus seq uence. It has been identified in 45.6% (2009/4406) of African American chromosom es from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs. washington.edu/EVS; dbSNP rs1348691). -

-

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

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 11, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Primary ciliary dyskinesia 3 Benign:2

Jan 12, 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

- -

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	-0.82
CADD	Benign	12
DANN	Benign	0.59
PhyloP100		1.1
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: rs1348691; hg19: chr5-13829608; COSMIC: COSV54258374;