Genetic Variant DNAI2:c.610+31G>A (chr17-74289767-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

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

The NM_023036.6(DNAI2):c.610+31G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 1,612,864 control chromosomes in the GnomAD database, including 18,846 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 1290 hom., cov: 31)

Exomes 𝑓: 0.15 ( 17556 hom. )

Consequence

DNAI2
NM_023036.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.918

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 (BayesDel_noAF=-0.81).

BP6

Variant 17-74289767-G-A is Benign according to our data. Variant chr17-74289767-G-A is described in ClinVar as [Benign]. Clinvar id is 261653.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.156 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAI2	NM_023036.6 link	c.610+31G>A		intron_variant	Intron 5 of 13	ENST00000311014.11	NP_075462.3	Q9GZS0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAI2	ENST00000311014.11 link	c.610+31G>A		intron_variant	Intron 5 of 13	1	NM_023036.6	ENSP00000308312.6		Q9GZS0-1

Frequencies

GnomAD3 genomes

AF:

0.121

AC:

18417

AN:

151924

Hom.:

1291

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0779

Gnomad AMI

AF:

0.115

Gnomad AMR

AF:

0.0823

Gnomad ASJ

AF:

0.119

Gnomad EAS

AF:

0.00367

Gnomad SAS

AF:

0.123

Gnomad FIN

AF:

0.172

Gnomad MID

AF:

0.0791

Gnomad NFE

AF:

0.158

Gnomad OTH

AF:

0.108

GnomAD3 exomes

AF:

0.124

AC:

30944

AN:

250198

Hom.:

2319

AF XY:

0.128

AC XY:

17347

AN XY:

135262

show subpopulations

Gnomad AFR exome

AF:

0.0804

Gnomad AMR exome

AF:

0.0559

Gnomad ASJ exome

AF:

0.108

Gnomad EAS exome

AF:

0.00283

Gnomad SAS exome

AF:

0.131

Gnomad FIN exome

AF:

0.173

Gnomad NFE exome

AF:

0.161

Gnomad OTH exome

AF:

0.123

GnomAD4 exome

AF:

0.150

AC:

219409

AN:

1460822

Hom.:

17556

Cov.:

AF XY:

0.151

AC XY:

109452

AN XY:

726686

show subpopulations

Gnomad4 AFR exome

AF:

0.0773

Gnomad4 AMR exome

AF:

0.0581

Gnomad4 ASJ exome

AF:

0.112

Gnomad4 EAS exome

AF:

0.00136

Gnomad4 SAS exome

AF:

0.133

Gnomad4 FIN exome

AF:

0.172

Gnomad4 NFE exome

AF:

0.164

Gnomad4 OTH exome

AF:

0.126

GnomAD4 genome

AF:

0.121

AC:

18431

AN:

152042

Hom.:

1290

Cov.:

AF XY:

0.120

AC XY:

8915

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.0780

Gnomad4 AMR

AF:

0.0821

Gnomad4 ASJ

AF:

0.119

Gnomad4 EAS

AF:

0.00368

Gnomad4 SAS

AF:

0.124

Gnomad4 FIN

AF:

0.172

Gnomad4 NFE

AF:

0.158

Gnomad4 OTH

AF:

0.107

Alfa

AF:

0.140

Hom.:

283

Bravo

AF:

0.112

Asia WGS

AF:

0.0560

AC:

197

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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_noAF

Benign

-0.81

CADD

Benign

7.6

DANN

Benign

0.65

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