17-74281740-A-G

Variant names:

• chr17-74281740-A-G
• rs3803792
• ENST00000579490.5:c.94A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_023036.6(DNAI2):​c.-11-67A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.35 in 1,520,768 control chromosomes in the GnomAD database, including 100,025 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.38 (11258 hom., cov: 31)
  • Exomes 𝑓: 0.35 (88767 hom.)
• Consequence: DNAI2 NM_023036.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.437
• Publications: 8 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.2974942E-6).
• BP6: Variant 17-74281740-A-G is Benign according to our data. Variant chr17-74281740-A-G is described in ClinVar as [Benign]. Clinvar id is 1184651.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.751 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAI2	NM_023036.6	c.-11-67A>G		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.-11-67A>G		intron_variant	Intron 1 of 13	1	NM_023036.6	ENSP00000308312.6

Frequencies

GnomAD3 genomes AF: 0.375 AC: 56966 AN: 151862 Hom.: 11237 Cov.: 31

Gnomad AFR AF: 0.374

Gnomad AMI AF: 0.288

Gnomad AMR AF: 0.463

Gnomad ASJ AF: 0.394

Gnomad EAS AF: 0.771

Gnomad SAS AF: 0.418

Gnomad FIN AF: 0.380

Gnomad MID AF: 0.547

Gnomad NFE AF: 0.320

Gnomad OTH AF: 0.409

GnomAD2 exomes AF: 0.405 AC: 96472 AN: 238332 AF XY: 0.395

Gnomad AFR exome AF: 0.384

Gnomad AMR exome AF: 0.526

Gnomad ASJ exome AF: 0.399

Gnomad EAS exome AF: 0.775

Gnomad FIN exome AF: 0.352

Gnomad NFE exome AF: 0.321

Gnomad OTH exome AF: 0.385

GnomAD4 exome AF: 0.347 AC: 475454 AN: 1368784 Hom.: 88767 Cov.: 22 AF XY: 0.348 AC XY: 238399 AN XY: 685378

African (AFR) AF: 0.378 AC: 11995 AN: 31770

American (AMR) AF: 0.520 AC: 23004 AN: 44246

Ashkenazi Jewish (ASJ) AF: 0.398 AC: 10174 AN: 25592

East Asian (EAS) AF: 0.796 AC: 31185 AN: 39162

South Asian (SAS) AF: 0.394 AC: 33340 AN: 84556

European-Finnish (FIN) AF: 0.353 AC: 15726 AN: 44584

Middle Eastern (MID) AF: 0.445 AC: 2380 AN: 5344

European-Non Finnish (NFE) AF: 0.314 AC: 325749 AN: 1036168

Other (OTH) AF: 0.382 AC: 21901 AN: 57362

GnomAD4 genome AF: 0.375 AC: 57016 AN: 151984 Hom.: 11258 Cov.: 31 AF XY: 0.383 AC XY: 28438 AN XY: 74282

African (AFR) AF: 0.374 AC: 15498 AN: 41450

American (AMR) AF: 0.463 AC: 7075 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.394 AC: 1368 AN: 3470

East Asian (EAS) AF: 0.771 AC: 3979 AN: 5160

South Asian (SAS) AF: 0.417 AC: 2006 AN: 4806

European-Finnish (FIN) AF: 0.380 AC: 4014 AN: 10570

Middle Eastern (MID) AF: 0.554 AC: 163 AN: 294

European-Non Finnish (NFE) AF: 0.321 AC: 21778 AN: 67948

Other (OTH) AF: 0.414 AC: 872 AN: 2108

Alfa AF: 0.346 Hom.: 15271

Bravo AF: 0.384

TwinsUK AF: 0.316 AC: 1170

ALSPAC AF: 0.320 AC: 1233

ExAC AF: 0.394 AC: 47789

Asia WGS AF: 0.599 AC: 2078 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Nov 11, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Primary ciliary dyskinesia 9 Benign:1

Jul 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.72	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	4.4
DANN	Benign	0.50
DEOGEN2	Benign	0.0058	T
FATHMM_MKL	Benign	0.00084	N
LIST_S2	Benign	0.23	T
MetaRNN	Benign	0.0000013	T
PhyloP100		0.44
Vest4		0.014
GERP RS		1.9
PromoterAI		-0.018	Neutral
Mutation Taster		=299/1	polymorphism (auto)

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: rs3803792; hg19: chr17-72277879; COSMIC: COSV56756811;