17-74274303-A-G

Position:

• chr17-74274303-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_023036.6(DNAI2):​c.-54A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.544 in 151,812 control chromosomes in the GnomAD database, including 22,861 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.54 (22853 hom., cov: 31)
  • Exomes 𝑓: 0.63 (8 hom.)
• Consequence: DNAI2 NM_023036.6 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.367

Genes affected

DNAI2 (HGNC:18744): (dynein axonemal intermediate chain 2) The protein encoded by this gene belongs to the dynein intermediate chain family, and is part of the dynein complex of respiratory cilia and sperm flagella. Mutations in this gene are associated with primary ciliary dyskinesia type 9. Alternatively spliced transcript variants encoding different isoforms have been noted for this gene. [provided by RefSeq, Mar 2010]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 17-74274303-A-G is Benign according to our data. Variant chr17-74274303-A-G is described in ClinVar as [Benign]. Clinvar id is 325001.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.78 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAI2	NM_023036.6	c.-54A>G		5_prime_UTR_variant	1/14	ENST00000311014.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAI2	ENST00000311014.11	c.-54A>G		5_prime_UTR_variant	1/14	1	NM_023036.6	P2
DNAI2	ENST00000582036.5	c.-51A>G		5_prime_UTR_variant	1/14	1
DNAI2	ENST00000579055.5	c.-54A>G		5_prime_UTR_variant, NMD_transcript_variant	1/13	2

Frequencies

GnomAD3 genomes AF: 0.543 AC: 82407 AN: 151652 Hom.: 22816 Cov.: 31

Gnomad AFR AF: 0.596

Gnomad AMI AF: 0.419

Gnomad AMR AF: 0.564

Gnomad ASJ AF: 0.517

Gnomad EAS AF: 0.800

Gnomad SAS AF: 0.609

Gnomad FIN AF: 0.549

Gnomad MID AF: 0.616

Gnomad NFE AF: 0.485

Gnomad OTH AF: 0.545

GnomAD4 exome AF: 0.625 AC: 25 AN: 40 Hom.: 8 Cov.: 0 AF XY: 0.676 AC XY: 23 AN XY: 34

Gnomad4 ASJ exome AF: 1.00

Gnomad4 FIN exome AF: 0.667

Gnomad4 NFE exome AF: 0.563

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.544 AC: 82492 AN: 151772 Hom.: 22853 Cov.: 31 AF XY: 0.549 AC XY: 40738 AN XY: 74160

Gnomad4 AFR AF: 0.596

Gnomad4 AMR AF: 0.565

Gnomad4 ASJ AF: 0.517

Gnomad4 EAS AF: 0.801

Gnomad4 SAS AF: 0.607

Gnomad4 FIN AF: 0.549

Gnomad4 NFE AF: 0.485

Gnomad4 OTH AF: 0.549

Alfa AF: 0.512 Hom.: 7800

Bravo AF: 0.546

Asia WGS AF: 0.719 AC: 2497 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Primary ciliary dyskinesia 9 Benign:1

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 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	-0.87
CADD	Benign	8.0
DANN	Benign	0.43

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: rs1877687; hg19: chr17-72270442;