dbSNP rs4239008: DNAI2:c.1722+34G>A (chr17-74312264-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.1722+34G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.844 in 506,342 control chromosomes in the GnomAD database, including 185,208 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.77 ( 47068 hom., cov: 26)

Exomes 𝑓: 0.87 ( 138140 hom. )

Consequence

DNAI2
NM_023036.6 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.201

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:

LOC105371891 (HGNC:):

LOC105371891 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=-0.85).

BP6

Variant 17-74312264-G-A is Benign according to our data. Variant chr17-74312264-G-A is described in ClinVar as [Benign]. Clinvar id is 261645.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.899 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAI2	NM_023036.6 link	c.1722+34G>A		intron_variant	Intron 12 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.1722+34G>A		intron_variant	Intron 12 of 13	1	NM_023036.6	ENSP00000308312.6		Q9GZS0-1

Frequencies

GnomAD3 genomes

AF:

0.769

AC:

114346

AN:

148656

Hom.:

47065

Cov.:

show subpopulations

Gnomad AFR

AF:

0.438

Gnomad AMI

AF:

0.881

Gnomad AMR

AF:

0.881

Gnomad ASJ

AF:

0.890

Gnomad EAS

AF:

0.845

Gnomad SAS

AF:

0.833

Gnomad FIN

AF:

0.880

Gnomad MID

AF:

0.842

Gnomad NFE

AF:

0.905

Gnomad OTH

AF:

0.788

GnomAD3 exomes

AF:

0.867

AC:

124824

AN:

144000

Hom.:

55094

AF XY:

0.869

AC XY:

67548

AN XY:

77774

show subpopulations

Gnomad AFR exome

AF:

0.415

Gnomad AMR exome

AF:

0.929

Gnomad ASJ exome

AF:

0.884

Gnomad EAS exome

AF:

0.852

Gnomad SAS exome

AF:

0.833

Gnomad FIN exome

AF:

0.889

Gnomad NFE exome

AF:

0.910

Gnomad OTH exome

AF:

0.883

GnomAD4 exome

AF:

0.875

AC:

312813

AN:

357586

Hom.:

138140

Cov.:

AF XY:

0.874

AC XY:

171097

AN XY:

195840

show subpopulations

Gnomad4 AFR exome

AF:

0.432

Gnomad4 AMR exome

AF:

0.926

Gnomad4 ASJ exome

AF:

0.882

Gnomad4 EAS exome

AF:

0.844

Gnomad4 SAS exome

AF:

0.833

Gnomad4 FIN exome

AF:

0.891

Gnomad4 NFE exome

AF:

0.905

Gnomad4 OTH exome

AF:

0.855

GnomAD4 genome

AF:

0.769

AC:

114357

AN:

148756

Hom.:

47068

Cov.:

AF XY:

0.771

AC XY:

55803

AN XY:

72336

show subpopulations

Gnomad4 AFR

AF:

0.438

Gnomad4 AMR

AF:

0.881

Gnomad4 ASJ

AF:

0.890

Gnomad4 EAS

AF:

0.845

Gnomad4 SAS

AF:

0.833

Gnomad4 FIN

AF:

0.880

Gnomad4 NFE

AF:

0.905

Gnomad4 OTH

AF:

0.786

Alfa

AF:

0.818

Hom.:

6398

Asia WGS

AF:

0.804

AC:

2792

AN:

3476

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

-0.85

CADD

Benign

6.2

DANN

Benign

0.75

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