17-74274284-GAGCCGCGACC-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_023036.6(DNAI2):c.-72_-63del variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.274 in 152,014 control chromosomes in the GnomAD database, including 7,254 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.27 (7252 hom., cov: 21)
  • Exomes 𝑓: 0.38 (2 hom.)
• Consequence: DNAI2 NM_023036.6 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.230

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 -10 ACMG points.

• BP6: Variant 17-74274284-GAGCCGCGACC-G is Benign according to our data. Variant chr17-74274284-GAGCCGCGACC-G is described in ClinVar as [Benign]. Clinvar id is 325000.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.756 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAI2	NM_023036.6	c.-72_-63del		5_prime_UTR_variant	1/14	ENST00000311014.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAI2	ENST00000311014.11	c.-72_-63del		5_prime_UTR_variant	1/14	1	NM_023036.6	P2
DNAI2	ENST00000582036.5	c.-69_-60del		5_prime_UTR_variant	1/14	1
DNAI2	ENST00000579055.5	c.-72_-63del		5_prime_UTR_variant, NMD_transcript_variant	1/13	2

Frequencies

GnomAD3 genomes AF: 0.274 AC: 41659 AN: 151862 Hom.: 7236 Cov.: 21

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.276

Gnomad AMR AF: 0.413

Gnomad ASJ AF: 0.372

Gnomad EAS AF: 0.776

Gnomad SAS AF: 0.389

Gnomad FIN AF: 0.345

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.284

Gnomad OTH AF: 0.318

GnomAD4 exome AF: 0.375 AC: 12 AN: 32 Hom.: 2 AF XY: 0.500 AC XY: 10 AN XY: 20

Gnomad4 ASJ exome AF: 0.500

Gnomad4 FIN exome AF: 0.375

Gnomad4 NFE exome AF: 0.300

Gnomad4 OTH exome AF: 0.300

GnomAD4 genome AF: 0.274 AC: 41685 AN: 151982 Hom.: 7252 Cov.: 21 AF XY: 0.286 AC XY: 21217 AN XY: 74272

Gnomad4 AFR AF: 0.101

Gnomad4 AMR AF: 0.414

Gnomad4 ASJ AF: 0.372

Gnomad4 EAS AF: 0.776

Gnomad4 SAS AF: 0.389

Gnomad4 FIN AF: 0.345

Gnomad4 NFE AF: 0.284

Gnomad4 OTH AF: 0.324

Alfa AF: 0.273 Hom.: 666

Bravo AF: 0.274

Asia WGS AF: 0.569 AC: 1975 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Primary ciliary dyskinesia Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs5822035; hg19: chr17-72270423; COSMIC: COSV56759144;