rs6554820

Positions:

• chr5-13850641-A-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.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:7
• Conservation: PhyloP100: -0.0310

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=-0.75).
• BP6: Variant 5-13850641-A-G is Benign according to our data. Variant chr5-13850641-A-G is described in ClinVar as [Benign]. Clinvar id is 163150.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-13850641-A-G is described in Lovd as [Benign].
• 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/exons	MANE	UniProt
DNAH5	NM_001369.3	c.5114+11T>C		intron_variant		ENST00000265104.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH5	ENST00000265104.5	c.5114+11T>C		intron_variant		1	NM_001369.3	P4
DNAH5	ENST00000681290.1	c.5069+11T>C		intron_variant				A1

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

GnomAD3 exomes AF: 0.384 AC: 96355 AN: 250974 Hom.: 19486 AF XY: 0.393 AC XY: 53261 AN XY: 135654

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 SAS exome AF: 0.477

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

Gnomad4 AFR exome AF: 0.306

Gnomad4 AMR exome AF: 0.283

Gnomad4 ASJ exome AF: 0.330

Gnomad4 EAS exome AF: 0.259

Gnomad4 SAS exome AF: 0.472

Gnomad4 FIN exome AF: 0.455

Gnomad4 NFE exome AF: 0.418

Gnomad4 OTH exome AF: 0.392

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

Gnomad4 AFR AF: 0.303

Gnomad4 AMR AF: 0.314

Gnomad4 ASJ AF: 0.324

Gnomad4 EAS AF: 0.263

Gnomad4 SAS AF: 0.470

Gnomad4 FIN AF: 0.463

Gnomad4 NFE AF: 0.422

Gnomad4 OTH AF: 0.379

Alfa AF: 0.401 Hom.: 16225

Bravo AF: 0.355

Asia WGS AF: 0.388 AC: 1352 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Primary ciliary dyskinesia 3 Benign:3

Benign, criteria provided, single submitter	clinical testing	Pars Genome Lab	Jun 15, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	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. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 30, 2021	- -

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Feb 21, 2013	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). -

Primary ciliary dyskinesia Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 11, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	8.3
DANN	Benign	0.69

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: rs6554820; hg19: chr5-13850750; COSMIC: COSV54227289;