rs10069041

chr5-13701247-T-C

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.13491+37A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.014 in 1,613,620 control chromosomes in the GnomAD database, including 1,927 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.065 (995 hom., cov: 32)
  • Exomes 𝑓: 0.0088 (932 hom.)
• Consequence: DNAH5 NM_001369.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.561

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=-0.59).
• BP6: Variant 5-13701247-T-C is Benign according to our data. Variant chr5-13701247-T-C is described in ClinVar as [Benign]. Clinvar id is 258000.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.213 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH5	NM_001369.3	c.13491+37A>G		intron_variant		ENST00000265104.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH5	ENST00000265104.5	c.13491+37A>G		intron_variant		1	NM_001369.3	P4
DNAH5	ENST00000681290.1	c.13446+37A>G		intron_variant				A1
DNAH5	ENST00000683611.1	n.824+37A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0647 AC: 9822 AN: 151918 Hom.: 990 Cov.: 32

Gnomad AFR AF: 0.216

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0312

Gnomad ASJ AF: 0.0153

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00935

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.00278

Gnomad OTH AF: 0.0475

GnomAD3 exomes AF: 0.0201 AC: 5029 AN: 249922 Hom.: 442 AF XY: 0.0167 AC XY: 2257 AN XY: 135532

Gnomad AFR exome AF: 0.224

Gnomad AMR exome AF: 0.0172

Gnomad ASJ exome AF: 0.0114

Gnomad EAS exome AF: 0.0000547

Gnomad SAS exome AF: 0.0112

Gnomad FIN exome AF: 0.0000925

Gnomad NFE exome AF: 0.00325

Gnomad OTH exome AF: 0.0168

GnomAD4 exome AF: 0.00877 AC: 12819 AN: 1461584 Hom.: 932 Cov.: 34 AF XY: 0.00824 AC XY: 5995 AN XY: 727128

Gnomad4 AFR exome AF: 0.221

Gnomad4 AMR exome AF: 0.0187

Gnomad4 ASJ exome AF: 0.0122

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0115

Gnomad4 FIN exome AF: 0.000131

Gnomad4 NFE exome AF: 0.00167

Gnomad4 OTH exome AF: 0.0186

GnomAD4 genome AF: 0.0648 AC: 9845 AN: 152036 Hom.: 995 Cov.: 32 AF XY: 0.0630 AC XY: 4681 AN XY: 74324

Gnomad4 AFR AF: 0.216

Gnomad4 AMR AF: 0.0312

Gnomad4 ASJ AF: 0.0153

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.00915

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00278

Gnomad4 OTH AF: 0.0470

Alfa AF: 0.0478 Hom.: 143

Bravo AF: 0.0735

Asia WGS AF: 0.0200 AC: 72 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

Feb 24, 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	-0.59
Cadd	Benign	12
Dann	Benign	0.64

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: rs10069041; hg19: chr5-13701356;