rs11958022

chr5-13865945-A-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.4117-39T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0394 in 1,316,114 control chromosomes in the GnomAD database, including 2,940 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.090 (1426 hom., cov: 33)
  • Exomes 𝑓: 0.033 (1514 hom.)
• Consequence: DNAH5 NM_001369.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.428

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=-0.82).
• BP6: Variant 5-13865945-A-C is Benign according to our data. Variant chr5-13865945-A-C is described in ClinVar as [Benign]. Clinvar id is 258030.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.248 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH5	NM_001369.3	c.4117-39T>G		intron_variant		ENST00000265104.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH5	ENST00000265104.5	c.4117-39T>G		intron_variant		1	NM_001369.3	P4
	ENST00000503244.2	n.253+5390A>C		intron_variant, non_coding_transcript_variant		4
DNAH5	ENST00000681290.1	c.4072-39T>G		intron_variant				A1
	ENST00000637153.1	n.213+5430A>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0900 AC: 13699 AN: 152146 Hom.: 1420 Cov.: 33

Gnomad AFR AF: 0.252

Gnomad AMI AF: 0.0417

Gnomad AMR AF: 0.0376

Gnomad ASJ AF: 0.0372

Gnomad EAS AF: 0.0705

Gnomad SAS AF: 0.0586

Gnomad FIN AF: 0.0227

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0219

Gnomad OTH AF: 0.0636

GnomAD3 exomes AF: 0.0466 AC: 11419 AN: 244792 Hom.: 671 AF XY: 0.0446 AC XY: 5938 AN XY: 133214

Gnomad AFR exome AF: 0.264

Gnomad AMR exome AF: 0.0183

Gnomad ASJ exome AF: 0.0394

Gnomad EAS exome AF: 0.0830

Gnomad SAS exome AF: 0.0634

Gnomad FIN exome AF: 0.0210

Gnomad NFE exome AF: 0.0219

Gnomad OTH exome AF: 0.0311

GnomAD4 exome AF: 0.0328 AC: 38138 AN: 1163850 Hom.: 1514 Cov.: 16 AF XY: 0.0330 AC XY: 19628 AN XY: 593914

Gnomad4 AFR exome AF: 0.255

Gnomad4 AMR exome AF: 0.0200

Gnomad4 ASJ exome AF: 0.0380

Gnomad4 EAS exome AF: 0.0639

Gnomad4 SAS exome AF: 0.0622

Gnomad4 FIN exome AF: 0.0215

Gnomad4 NFE exome AF: 0.0221

Gnomad4 OTH exome AF: 0.0404

GnomAD4 genome AF: 0.0902 AC: 13728 AN: 152264 Hom.: 1426 Cov.: 33 AF XY: 0.0885 AC XY: 6591 AN XY: 74460

Gnomad4 AFR AF: 0.252

Gnomad4 AMR AF: 0.0376

Gnomad4 ASJ AF: 0.0372

Gnomad4 EAS AF: 0.0705

Gnomad4 SAS AF: 0.0580

Gnomad4 FIN AF: 0.0227

Gnomad4 NFE AF: 0.0219

Gnomad4 OTH AF: 0.0634

Alfa AF: 0.0401 Hom.: 222

Bravo AF: 0.0986

Asia WGS AF: 0.0720 AC: 251 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

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

Dec 31, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	0.21
Dann	Benign	0.56

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: rs11958022; hg19: chr5-13866054;