chr5-13690482-G-A

Position:

• chr5-13690482-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001369.3(DNAH5):​c.*1502C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00938 in 152,280 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0094 (11 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: DNAH5 NM_001369.3 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.378

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=-0.87).
• BP6: Variant 5-13690482-G-A is Benign according to our data. Variant chr5-13690482-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 350904.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00938 (1428/152280) while in subpopulation EAS AF= 0.045 (233/5178). AF 95% confidence interval is 0.0403. There are 11 homozygotes in gnomad4. There are 701 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH5	NM_001369.3	c.*1502C>T		3_prime_UTR_variant	79/79	ENST00000265104.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH5	ENST00000265104.5	c.*1502C>T		3_prime_UTR_variant	79/79	1	NM_001369.3	P4
DNAH5	ENST00000681290.1	c.*1502C>T		3_prime_UTR_variant	79/79			A1
DNAH5	ENST00000683611.1	n.2710C>T		non_coding_transcript_exon_variant	5/5

Frequencies

GnomAD3 genomes AF: 0.00940 AC: 1430 AN: 152162 Hom.: 10 Cov.: 32

Gnomad AFR AF: 0.00326

Gnomad AMI AF: 0.0198

Gnomad AMR AF: 0.00432

Gnomad ASJ AF: 0.0144

Gnomad EAS AF: 0.0453

Gnomad SAS AF: 0.0191

Gnomad FIN AF: 0.00679

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0108

Gnomad OTH AF: 0.00908

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.00938 AC: 1428 AN: 152280 Hom.: 11 Cov.: 32 AF XY: 0.00942 AC XY: 701 AN XY: 74442

Gnomad4 AFR AF: 0.00325

Gnomad4 AMR AF: 0.00431

Gnomad4 ASJ AF: 0.0144

Gnomad4 EAS AF: 0.0450

Gnomad4 SAS AF: 0.0189

Gnomad4 FIN AF: 0.00679

Gnomad4 NFE AF: 0.0108

Gnomad4 OTH AF: 0.00946

Alfa AF: 0.00860 Hom.: 0

Bravo AF: 0.00882

Asia WGS AF: 0.0250 AC: 87 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Primary ciliary dyskinesia 3 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.5
DANN	Benign	0.52

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: rs144265705; hg19: chr5-13690591;