17-74281550-G-A

Variant summary

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

The ENST00000579490.5(DNAI2):c.-97G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 585,530 control chromosomes in the GnomAD database, including 5,367 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.12 (1171 hom., cov: 31)
  • Exomes 𝑓: 0.13 (4196 hom.)
• Consequence: DNAI2 ENST00000579490.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.365

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=-0.93).
• BP6: Variant 17-74281550-G-A is Benign according to our data. Variant chr17-74281550-G-A is described in ClinVar as [Benign]. Clinvar id is 1249367.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.149 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAI2	NM_023036.6	c.-11-257G>A		intron_variant		ENST00000311014.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAI2	ENST00000311014.11	c.-11-257G>A		intron_variant		1	NM_023036.6	P2

Frequencies

GnomAD3 genomes AF: 0.116 AC: 17614 AN: 152010 Hom.: 1172 Cov.: 31

Gnomad AFR AF: 0.0749

Gnomad AMI AF: 0.117

Gnomad AMR AF: 0.0742

Gnomad ASJ AF: 0.0956

Gnomad EAS AF: 0.00212

Gnomad SAS AF: 0.116

Gnomad FIN AF: 0.172

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.152

Gnomad OTH AF: 0.0964

GnomAD4 exome AF: 0.129 AC: 55972 AN: 433402 Hom.: 4196 Cov.: 3 AF XY: 0.130 AC XY: 29307 AN XY: 226244

Gnomad4 AFR exome AF: 0.0734

Gnomad4 AMR exome AF: 0.0607

Gnomad4 ASJ exome AF: 0.0912

Gnomad4 EAS exome AF: 0.000683

Gnomad4 SAS exome AF: 0.125

Gnomad4 FIN exome AF: 0.168

Gnomad4 NFE exome AF: 0.151

Gnomad4 OTH exome AF: 0.114

GnomAD4 genome AF: 0.116 AC: 17623 AN: 152128 Hom.: 1171 Cov.: 31 AF XY: 0.115 AC XY: 8518 AN XY: 74350

Gnomad4 AFR AF: 0.0751

Gnomad4 AMR AF: 0.0740

Gnomad4 ASJ AF: 0.0956

Gnomad4 EAS AF: 0.00212

Gnomad4 SAS AF: 0.116

Gnomad4 FIN AF: 0.172

Gnomad4 NFE AF: 0.152

Gnomad4 OTH AF: 0.0954

Alfa AF: 0.0698 Hom.: 85

Bravo AF: 0.106

Asia WGS AF: 0.0550 AC: 193 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 11, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	2.5
Dann	Benign	0.42

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: rs62065702; hg19: chr17-72277689;