5-13690936-T-C

Position:

• chr5-13690936-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.*1048A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.494 in 151,952 control chromosomes in the GnomAD database, including 18,870 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.49 (18870 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: DNAH5 NM_001369.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0750

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=-0.82).
• BP6: Variant 5-13690936-T-C is Benign according to our data. Variant chr5-13690936-T-C is described in ClinVar as [Benign]. Clinvar id is 350910.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.536 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH5	NM_001369.3	c.*1048A>G		3_prime_UTR_variant	79/79	ENST00000265104.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH5	ENST00000265104.5	c.*1048A>G		3_prime_UTR_variant	79/79	1	NM_001369.3	P4
DNAH5	ENST00000681290.1	c.*1048A>G		3_prime_UTR_variant	79/79			A1
DNAH5	ENST00000683611.1	n.2256A>G		non_coding_transcript_exon_variant	5/5

Frequencies

GnomAD3 genomes AF: 0.494 AC: 75005 AN: 151832 Hom.: 18864 Cov.: 32

Gnomad AFR AF: 0.419

Gnomad AMI AF: 0.567

Gnomad AMR AF: 0.502

Gnomad ASJ AF: 0.527

Gnomad EAS AF: 0.395

Gnomad SAS AF: 0.419

Gnomad FIN AF: 0.537

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.541

Gnomad OTH AF: 0.507

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: 0.494 AC: 75051 AN: 151952 Hom.: 18870 Cov.: 32 AF XY: 0.490 AC XY: 36356 AN XY: 74262

Gnomad4 AFR AF: 0.419

Gnomad4 AMR AF: 0.502

Gnomad4 ASJ AF: 0.527

Gnomad4 EAS AF: 0.395

Gnomad4 SAS AF: 0.419

Gnomad4 FIN AF: 0.537

Gnomad4 NFE AF: 0.541

Gnomad4 OTH AF: 0.508

Alfa AF: 0.503 Hom.: 3690

Bravo AF: 0.492

Asia WGS AF: 0.427 AC: 1483 AN: 3468

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Primary ciliary dyskinesia 3 Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.9
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: rs2896111; hg19: chr5-13691045;