Genetic Variant DNAI2:c.725-27C>T (chr17-74299691-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_023036.6(DNAI2):c.725-27C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.037 in 1,612,962 control chromosomes in the GnomAD database, including 1,381 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.027 ( 85 hom., cov: 32)

Exomes 𝑓: 0.038 ( 1296 hom. )

Consequence

DNAI2
NM_023036.6 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.688

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 17-74299691-C-T is Benign according to our data. Variant chr17-74299691-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 261654.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0269 (4104/152284) while in subpopulation NFE AF= 0.0408 (2773/68020). AF 95% confidence interval is 0.0395. There are 85 homozygotes in gnomad4. There are 1976 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 85 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAI2	NM_023036.6 link	c.725-27C>T		intron_variant	Intron 6 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.725-27C>T		intron_variant	Intron 6 of 13	1	NM_023036.6	ENSP00000308312.6		Q9GZS0-1

Frequencies

GnomAD3 genomes

AF:

0.0270

AC:

4103

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00688

Gnomad AMI

AF:

0.0987

Gnomad AMR

AF:

0.0168

Gnomad ASJ

AF:

0.00432

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00539

Gnomad FIN

AF:

0.0588

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0407

Gnomad OTH

AF:

0.0163

GnomAD3 exomes

AF:

0.0265

AC:

6609

AN:

249632

Hom.:

126

AF XY:

0.0270

AC XY:

3650

AN XY:

135156

show subpopulations

Gnomad AFR exome

AF:

0.00643

Gnomad AMR exome

AF:

0.00865

Gnomad ASJ exome

AF:

0.00408

Gnomad EAS exome

AF:

0.0000545

Gnomad SAS exome

AF:

0.00516

Gnomad FIN exome

AF:

0.0607

Gnomad NFE exome

AF:

0.0405

Gnomad OTH exome

AF:

0.0265

GnomAD4 exome

AF:

0.0380

AC:

55506

AN:

1460678

Hom.:

1296

Cov.:

AF XY:

0.0370

AC XY:

26855

AN XY:

726602

show subpopulations

Gnomad4 AFR exome

AF:

0.00556

Gnomad4 AMR exome

AF:

0.00962

Gnomad4 ASJ exome

AF:

0.00444

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00598

Gnomad4 FIN exome

AF:

0.0603

Gnomad4 NFE exome

AF:

0.0442

Gnomad4 OTH exome

AF:

0.0322

GnomAD4 genome

AF:

0.0269

AC:

4104

AN:

152284

Hom.:

Cov.:

AF XY:

0.0265

AC XY:

1976

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.00686

Gnomad4 AMR

AF:

0.0167

Gnomad4 ASJ

AF:

0.00432

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00539

Gnomad4 FIN

AF:

0.0588

Gnomad4 NFE

AF:

0.0408

Gnomad4 OTH

AF:

0.0161

Alfa

AF:

0.0294

Hom.:

Bravo

AF:

0.0235

Asia WGS

AF:

0.00375

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 21, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Likely 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

-0.82

CADD

Benign

2.5

DANN

Benign

0.58

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