rs1530495

Positions:

• chr5-13932008-A-G
• chr5-13932008-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001369.3(DNAH5):​c.58-764T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.41 in 152,148 control chromosomes in the GnomAD database, including 14,396 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.41 (14393 hom., cov: 33)
  • Exomes 𝑓: 0.18 (3 hom.)
• Consequence: DNAH5 NM_001369.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.09

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.679 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH5	NM_001369.3	c.58-764T>C		intron_variant		ENST00000265104.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH5	ENST00000265104.5	c.58-764T>C		intron_variant		1	NM_001369.3	P4

Frequencies

GnomAD3 genomes AF: 0.410 AC: 62238 AN: 151964 Hom.: 14370 Cov.: 33

Gnomad AFR AF: 0.607

Gnomad AMI AF: 0.273

Gnomad AMR AF: 0.396

Gnomad ASJ AF: 0.346

Gnomad EAS AF: 0.698

Gnomad SAS AF: 0.376

Gnomad FIN AF: 0.284

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.298

Gnomad OTH AF: 0.407

GnomAD4 exome AF: 0.182 AC: 12 AN: 66 Hom.: 3 Cov.: 0 AF XY: 0.239 AC XY: 11 AN XY: 46

Gnomad4 AMR exome AF: 0.00

Gnomad4 EAS exome AF: 1.00

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.161

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.410 AC: 62310 AN: 152082 Hom.: 14393 Cov.: 33 AF XY: 0.408 AC XY: 30361 AN XY: 74342

Gnomad4 AFR AF: 0.607

Gnomad4 AMR AF: 0.397

Gnomad4 ASJ AF: 0.346

Gnomad4 EAS AF: 0.698

Gnomad4 SAS AF: 0.375

Gnomad4 FIN AF: 0.284

Gnomad4 NFE AF: 0.298

Gnomad4 OTH AF: 0.407

Alfa AF: 0.352 Hom.: 1772

Bravo AF: 0.427

Asia WGS AF: 0.515 AC: 1787 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.13
DANN	Benign	0.31

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: rs1530495; hg19: chr5-13932117;