ENST00000579490.5:c.-41G>C

Variant names:

• chr17-74281606-G-C
• rs73996949
• ENST00000579490.5:c.-41G>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The ENST00000579490.5(DNAI2):​c.-41G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00327 in 615,722 control chromosomes in the GnomAD database, including 28 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0096 (19 hom., cov: 31)
  • Exomes 𝑓: 0.0012 (9 hom.)
• Consequence: DNAI2 ENST00000579490.5 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.29
• Publications: 0 publications found

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]

DNAI2 Gene-Disease associations (from GenCC):

• primary ciliary dyskinesia 9

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), ClinGen
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 17-74281606-G-C is Benign according to our data. Variant chr17-74281606-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 1706936.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00961 (1463/152192) while in subpopulation AFR AF = 0.0335 (1392/41526). AF 95% confidence interval is 0.0321. There are 19 homozygotes in GnomAd4. There are 667 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 19 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAI2	NM_023036.6	c.-11-201G>C		intron_variant	Intron 1 of 13	ENST00000311014.11	NP_075462.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAI2	ENST00000311014.11	c.-11-201G>C		intron_variant	Intron 1 of 13	1	NM_023036.6	ENSP00000308312.6

Frequencies

GnomAD3 genomes AF: 0.00956 AC: 1454 AN: 152074 Hom.: 19 Cov.: 31

Gnomad AFR AF: 0.0334

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00354

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00623

GnomAD2 exomes AF: 0.00348 AC: 209 AN: 59988 AF XY: 0.00316

Gnomad AFR exome AF: 0.0339

Gnomad AMR exome AF: 0.00159

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000127

Gnomad OTH exome AF: 0.00196

GnomAD4 exome AF: 0.00118 AC: 549 AN: 463530 Hom.: 9 Cov.: 5 AF XY: 0.00101 AC XY: 246 AN XY: 243670

African (AFR) AF: 0.0317 AC: 403 AN: 12728

American (AMR) AF: 0.00219 AC: 43 AN: 19592

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13988

East Asian (EAS) AF: 0.00 AC: 0 AN: 31244

South Asian (SAS) AF: 0.0000849 AC: 4 AN: 47122

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29634

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2010

European-Non Finnish (NFE) AF: 0.0000855 AC: 24 AN: 280716

Other (OTH) AF: 0.00283 AC: 75 AN: 26496

GnomAD4 genome AF: 0.00961 AC: 1463 AN: 152192 Hom.: 19 Cov.: 31 AF XY: 0.00896 AC XY: 667 AN XY: 74406

African (AFR) AF: 0.0335 AC: 1392 AN: 41526

American (AMR) AF: 0.00354 AC: 54 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4810

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68028

Other (OTH) AF: 0.00616 AC: 13 AN: 2110

Alfa AF: 0.00146 Hom.: 0

Bravo AF: 0.0106

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

May 27, 2021

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

See Variant Classification Assertion Criteria. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.089
DANN	Benign	0.42
PhyloP100		-1.3
PromoterAI		0.012	Neutral
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs73996949; hg19: chr17-72277745;