rs10041099

Positions:

• chr5-13845042-C-G
• chr5-13845042-C-T

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.5115-49G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.362 in 1,580,278 control chromosomes in the GnomAD database, including 105,419 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.40 (12616 hom., cov: 32)
  • Exomes 𝑓: 0.36 (92803 hom.)
• Consequence: DNAH5 NM_001369.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.231

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=-0.86).
• BP6: Variant 5-13845042-C-G is Benign according to our data. Variant chr5-13845042-C-G is described in ClinVar as [Benign]. Clinvar id is 258041.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.59 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH5	NM_001369.3	c.5115-49G>C		intron_variant		ENST00000265104.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH5	ENST00000265104.5	c.5115-49G>C		intron_variant		1	NM_001369.3	P4
DNAH5	ENST00000681290.1	c.5070-49G>C		intron_variant				A1

Frequencies

GnomAD3 genomes AF: 0.401 AC: 60871 AN: 151728 Hom.: 12597 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: 0.608

Gnomad SAS AF: 0.349

Gnomad FIN AF: 0.316

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.353

Gnomad OTH AF: 0.399

GnomAD3 exomes AF: 0.376 AC: 89974 AN: 239400 Hom.: 17488 AF XY: 0.370 AC XY: 48186 AN XY: 130360

Gnomad AFR exome AF: 0.498

Gnomad AMR exome AF: 0.359

Gnomad ASJ exome AF: 0.340

Gnomad EAS exome AF: 0.629

Gnomad SAS exome AF: 0.338

Gnomad FIN exome AF: 0.319

Gnomad NFE exome AF: 0.348

Gnomad OTH exome AF: 0.367

GnomAD4 exome AF: 0.357 AC: 510369 AN: 1428432 Hom.: 92803 Cov.: 24 AF XY: 0.356 AC XY: 253454 AN XY: 712376

Gnomad4 AFR exome AF: 0.495

Gnomad4 AMR exome AF: 0.366

Gnomad4 ASJ exome AF: 0.338

Gnomad4 EAS exome AF: 0.559

Gnomad4 SAS exome AF: 0.337

Gnomad4 FIN exome AF: 0.326

Gnomad4 NFE exome AF: 0.349

Gnomad4 OTH exome AF: 0.368

GnomAD4 genome AF: 0.401 AC: 60932 AN: 151846 Hom.: 12616 Cov.: 32 AF XY: 0.398 AC XY: 29550 AN XY: 74210

Gnomad4 AFR AF: 0.499

Gnomad4 AMR AF: 0.371

Gnomad4 ASJ AF: 0.347

Gnomad4 EAS AF: 0.608

Gnomad4 SAS AF: 0.348

Gnomad4 FIN AF: 0.316

Gnomad4 NFE AF: 0.353

Gnomad4 OTH AF: 0.397

Alfa AF: 0.295 Hom.: 1139

Bravo AF: 0.413

Asia WGS AF: 0.454 AC: 1576 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 11, 2018

- -

Primary ciliary dyskinesia 3 Benign:1

Benign, criteria provided, single submitter

clinical testing

Pars Genome Lab

Jun 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.3
DANN	Benign	0.30

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: rs10041099; hg19: chr5-13845151; COSMIC: COSV54244753;