rs4701988

chr5-13850630-T-Achr5-13850630-T-Cchr5-13850630-T-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+22A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.385 in 1,608,968 control chromosomes in the GnomAD database, including 122,568 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.35 (9747 hom., cov: 33)
  • Exomes 𝑓: 0.39 (112821 hom.)
• Consequence: DNAH5 NM_001369.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.858

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=-0.78).
• BP6: Variant 5-13850630-T-A is Benign according to our data. Variant chr5-13850630-T-A is described in ClinVar as [Benign]. Clinvar id is 258038.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.563 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH5	NM_001369.3	c.5114+22A>T		intron_variant		ENST00000265104.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH5	ENST00000265104.5	c.5114+22A>T		intron_variant		1	NM_001369.3	P4
DNAH5	ENST00000681290.1	c.5069+22A>T		intron_variant				A1

Frequencies

GnomAD3 genomes AF: 0.347 AC: 52752 AN: 152028 Hom.: 9750 Cov.: 33

Gnomad AFR AF: 0.210

Gnomad AMI AF: 0.453

Gnomad AMR AF: 0.406

Gnomad ASJ AF: 0.484

Gnomad EAS AF: 0.580

Gnomad SAS AF: 0.318

Gnomad FIN AF: 0.336

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.393

Gnomad OTH AF: 0.387

GnomAD3 exomes AF: 0.388 AC: 97255 AN: 250900 Hom.: 19873 AF XY: 0.388 AC XY: 52647 AN XY: 135624

Gnomad AFR exome AF: 0.206

Gnomad AMR exome AF: 0.400

Gnomad ASJ exome AF: 0.479

Gnomad EAS exome AF: 0.595

Gnomad SAS exome AF: 0.307

Gnomad FIN exome AF: 0.342

Gnomad NFE exome AF: 0.396

Gnomad OTH exome AF: 0.422

GnomAD4 exome AF: 0.389 AC: 566610 AN: 1456822 Hom.: 112821 Cov.: 30 AF XY: 0.388 AC XY: 281191 AN XY: 725124

Gnomad4 AFR exome AF: 0.200

Gnomad4 AMR exome AF: 0.401

Gnomad4 ASJ exome AF: 0.479

Gnomad4 EAS exome AF: 0.584

Gnomad4 SAS exome AF: 0.310

Gnomad4 FIN exome AF: 0.348

Gnomad4 NFE exome AF: 0.392

Gnomad4 OTH exome AF: 0.397

GnomAD4 genome AF: 0.347 AC: 52753 AN: 152146 Hom.: 9747 Cov.: 33 AF XY: 0.349 AC XY: 25938 AN XY: 74362

Gnomad4 AFR AF: 0.210

Gnomad4 AMR AF: 0.406

Gnomad4 ASJ AF: 0.484

Gnomad4 EAS AF: 0.580

Gnomad4 SAS AF: 0.317

Gnomad4 FIN AF: 0.336

Gnomad4 NFE AF: 0.393

Gnomad4 OTH AF: 0.386

Alfa AF: 0.292 Hom.: 1204

Bravo AF: 0.352

Asia WGS AF: 0.410 AC: 1426 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

Apr 04, 2019

- -

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	-0.78
Cadd	Benign	8.8
Dann	Benign	0.75

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: rs4701988; hg19: chr5-13850739; COSMIC: COSV54208540;