rs13156044

chr5-13867742-G-A

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.4053+32C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 1,559,750 control chromosomes in the GnomAD database, including 11,943 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (1162 hom., cov: 32)
  • Exomes 𝑓: 0.12 (10781 hom.)
• Consequence: DNAH5 NM_001369.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.890

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 5-13867742-G-A is Benign according to our data. Variant chr5-13867742-G-A is described in ClinVar as [Benign]. Clinvar id is 258027.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-13867742-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.129 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH5	NM_001369.3	c.4053+32C>T		intron_variant		ENST00000265104.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH5	ENST00000265104.5	c.4053+32C>T		intron_variant		1	NM_001369.3	P4
	ENST00000503244.2	n.253+7187G>A		intron_variant, non_coding_transcript_variant		4
DNAH5	ENST00000681290.1	c.4008+32C>T		intron_variant				A1
	ENST00000637153.1	n.213+7227G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.121 AC: 18369 AN: 151944 Hom.: 1160 Cov.: 32

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.0559

Gnomad AMR AF: 0.0755

Gnomad ASJ AF: 0.0703

Gnomad EAS AF: 0.103

Gnomad SAS AF: 0.0469

Gnomad FIN AF: 0.174

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.131

Gnomad OTH AF: 0.109

GnomAD3 exomes AF: 0.107 AC: 26599 AN: 249558 Hom.: 1604 AF XY: 0.105 AC XY: 14179 AN XY: 134924

Gnomad AFR exome AF: 0.120

Gnomad AMR exome AF: 0.0495

Gnomad ASJ exome AF: 0.0737

Gnomad EAS exome AF: 0.0990

Gnomad SAS exome AF: 0.0490

Gnomad FIN exome AF: 0.167

Gnomad NFE exome AF: 0.130

Gnomad OTH exome AF: 0.111

GnomAD4 exome AF: 0.120 AC: 169031 AN: 1407686 Hom.: 10781 Cov.: 25 AF XY: 0.118 AC XY: 82873 AN XY: 703590

Gnomad4 AFR exome AF: 0.126

Gnomad4 AMR exome AF: 0.0543

Gnomad4 ASJ exome AF: 0.0732

Gnomad4 EAS exome AF: 0.0915

Gnomad4 SAS exome AF: 0.0496

Gnomad4 FIN exome AF: 0.168

Gnomad4 NFE exome AF: 0.128

Gnomad4 OTH exome AF: 0.118

GnomAD4 genome AF: 0.121 AC: 18381 AN: 152064 Hom.: 1162 Cov.: 32 AF XY: 0.119 AC XY: 8819 AN XY: 74308

Gnomad4 AFR AF: 0.125

Gnomad4 AMR AF: 0.0754

Gnomad4 ASJ AF: 0.0703

Gnomad4 EAS AF: 0.104

Gnomad4 SAS AF: 0.0474

Gnomad4 FIN AF: 0.174

Gnomad4 NFE AF: 0.131

Gnomad4 OTH AF: 0.108

Alfa AF: 0.119 Hom.: 1341

Bravo AF: 0.113

Asia WGS AF: 0.0880 AC: 306 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 10, 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	-0.90
Cadd	Benign	0.053
Dann	Benign	0.71

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: rs13156044; hg19: chr5-13867851; COSMIC: COSV54243568;