rs6554820

Variant names:

• chr5-13850641-A-G
• rs6554820
• NM_001369.3:c.5114+11T>C

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.5114+11T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.405 in 1,611,744 control chromosomes in the GnomAD database, including 134,911 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.37 (10926 hom., cov: 32)
  • Exomes 𝑓: 0.41 (123985 hom.)
• Consequence: DNAH5 NM_001369.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -0.0310
• Publications: 7 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=-0.75).
• BP6: Variant 5-13850641-A-G is Benign according to our data. Variant chr5-13850641-A-G is described in ClinVar as Benign. ClinVar VariationId is 163150.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.454 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH5	NM_001369.3	c.5114+11T>C		intron_variant	Intron 31 of 78	ENST00000265104.5	NP_001360.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH5	ENST00000265104.5	c.5114+11T>C		intron_variant	Intron 31 of 78	1	NM_001369.3	ENSP00000265104.4
DNAH5	ENST00000681290.1	c.5069+11T>C		intron_variant	Intron 31 of 78			ENSP00000505288.1

Frequencies

GnomAD3 genomes AF: 0.374 AC: 56828 AN: 152042 Hom.: 10906 Cov.: 32

Gnomad AFR AF: 0.303

Gnomad AMI AF: 0.331

Gnomad AMR AF: 0.314

Gnomad ASJ AF: 0.324

Gnomad EAS AF: 0.261

Gnomad SAS AF: 0.468

Gnomad FIN AF: 0.463

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.422

Gnomad OTH AF: 0.375

GnomAD2 exomes AF: 0.384 AC: 96355 AN: 250974 AF XY: 0.393

Gnomad AFR exome AF: 0.294

Gnomad AMR exome AF: 0.275

Gnomad ASJ exome AF: 0.331

Gnomad EAS exome AF: 0.239

Gnomad FIN exome AF: 0.455

Gnomad NFE exome AF: 0.420

Gnomad OTH exome AF: 0.373

GnomAD4 exome AF: 0.409 AC: 596546 AN: 1459584 Hom.: 123985 Cov.: 34 AF XY: 0.411 AC XY: 298258 AN XY: 726280

African (AFR) AF: 0.306 AC: 10245 AN: 33430

American (AMR) AF: 0.283 AC: 12645 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.330 AC: 8620 AN: 26128

East Asian (EAS) AF: 0.259 AC: 10276 AN: 39658

South Asian (SAS) AF: 0.472 AC: 40653 AN: 86178

European-Finnish (FIN) AF: 0.455 AC: 24278 AN: 53394

Middle Eastern (MID) AF: 0.339 AC: 1906 AN: 5618

European-Non Finnish (NFE) AF: 0.418 AC: 464247 AN: 1110140

Other (OTH) AF: 0.392 AC: 23676 AN: 60326

GnomAD4 genome AF: 0.374 AC: 56890 AN: 152160 Hom.: 10926 Cov.: 32 AF XY: 0.373 AC XY: 27763 AN XY: 74392

African (AFR) AF: 0.303 AC: 12578 AN: 41518

American (AMR) AF: 0.314 AC: 4805 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.324 AC: 1122 AN: 3468

East Asian (EAS) AF: 0.263 AC: 1361 AN: 5178

South Asian (SAS) AF: 0.470 AC: 2257 AN: 4804

European-Finnish (FIN) AF: 0.463 AC: 4903 AN: 10598

Middle Eastern (MID) AF: 0.354 AC: 104 AN: 294

European-Non Finnish (NFE) AF: 0.422 AC: 28659 AN: 67984

Other (OTH) AF: 0.379 AC: 799 AN: 2110

Alfa AF: 0.398 Hom.: 27373

Bravo AF: 0.355

Asia WGS AF: 0.388 AC: 1352 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Primary ciliary dyskinesia 3 Benign:3

Jun 15, 2021

Pars Genome Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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. -

Jul 30, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:2

-

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

5114+11T>C in intron 31 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 41.7% (3583/8600) of European American chromoso mes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs .washington.edu/EVS; dbSNP rs6554820). -

not provided Benign:2

Nov 11, 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	-0.75
CADD	Benign	8.3
DANN	Benign	0.69
PhyloP100		-0.031
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: rs6554820; hg19: chr5-13850750; COSMIC: COSV54227289;