Variant 17-74281740-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000579490.5(DNAI2):c.94A>G(p.Arg32Gly) variant causes a missense 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. 9/10 in silico tools predict 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
ENST00000579490.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.437

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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. Variant chr17-74281740-A-G is described in Lovd as [Benign].

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/exons	MANE	Protein	UniProt
DNAI2	NM_023036.6 link	c.-11-67A>G		intron_variant		ENST00000311014.11	NP_075462.3	Q9GZS0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAI2	ENST00000311014.11 link	c.-11-67A>G		intron_variant		1	NM_023036.6	ENSP00000308312.6		Q9GZS0-1

Frequencies

GnomAD3 genomes

AF:

0.375

AC:

56966

AN:

151862

Hom.:

11237

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.405

AC:

96472

AN:

238332

Hom.:

21369

AF XY:

0.395

AC XY:

51378

AN XY:

130078

show subpopulations

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 SAS exome

AF:

0.394

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.:

AF XY:

0.348

AC XY:

238399

AN XY:

685378

show subpopulations

Gnomad4 AFR exome

AF:

0.378

Gnomad4 AMR exome

AF:

0.520

Gnomad4 ASJ exome

AF:

0.398

Gnomad4 EAS exome

AF:

0.796

Gnomad4 SAS exome

AF:

0.394

Gnomad4 FIN exome

AF:

0.353

Gnomad4 NFE exome

AF:

0.314

Gnomad4 OTH exome

AF:

0.382

GnomAD4 genome

AF:

0.375

AC:

57016

AN:

151984

Hom.:

11258

Cov.:

AF XY:

0.383

AC XY:

28438

AN XY:

74282

show subpopulations

Gnomad4 AFR

AF:

0.374

Gnomad4 AMR

AF:

0.463

Gnomad4 ASJ

AF:

0.394

Gnomad4 EAS

AF:

0.771

Gnomad4 SAS

AF:

0.417

Gnomad4 FIN

AF:

0.380

Gnomad4 NFE

AF:

0.321

Gnomad4 OTH

AF:

0.414

Alfa

AF:

0.343

Hom.:

11646

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

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 11, 2018	- -

Primary ciliary dyskinesia 9

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.67

CADD

Benign

4.4

DANN

Benign

0.50

DEOGEN2

Benign

0.0058

FATHMM_MKL

Benign

0.00084

LIST_S2

Benign

0.23

MetaRNN

Benign

0.0000013

Vest4

0.014

GERP RS

1.9

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over