dbSNP rs140326154: DNAI2:p.Val252Met (chr17-74299747-G-A) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBP6

The NM_023036.6(DNAI2):c.754G>A(p.Val252Met) variant causes a missense change. The variant allele was found at a frequency of 0.000162 in 1,613,438 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00083 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000092 ( 0 hom. )

Consequence

DNAI2
NM_023036.6 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:4B:4

Conservation

PhyloP100: 4.34

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

primary ciliary dyskinesia 9
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae)
primary ciliary dyskinesia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

DNAI2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.014344245).

BP6

Variant 17-74299747-G-A is Benign according to our data. Variant chr17-74299747-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 261656.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_023036.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DNAI2	NM_023036.6	MANE Select	c.754G>A	p.Val252Met	missense	Exon 7 of 14	NP_075462.3	Q9GZS0-1
DNAI2	NM_001353167.2		c.754G>A	p.Val252Met	missense	Exon 7 of 15	NP_001340096.1
DNAI2	NM_001172810.3		c.754G>A	p.Val252Met	missense	Exon 7 of 14	NP_001166281.1	Q9GZS0-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DNAI2	ENST00000311014.11	TSL:1 MANE Select	c.754G>A	p.Val252Met	missense	Exon 7 of 14	ENSP00000308312.6	Q9GZS0-1
DNAI2	ENST00000579490.5	TSL:1	c.925G>A	p.Val309Met	missense	Exon 6 of 13	ENSP00000464197.1	J3QRG2
DNAI2	ENST00000446837.2	TSL:1	c.754G>A	p.Val252Met	missense	Exon 6 of 13	ENSP00000400252.2	Q9GZS0-1

Frequencies

GnomAD3 genomes

AF:

0.000835

AC:

127

AN:

152060

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00261

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00143

GnomAD2 exomes

AF:

0.000219

AC:

AN:

250616

AF XY:

0.000133

show subpopulations

Gnomad AFR exome

AF:

0.00302

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000924

AC:

135

AN:

1461260

Hom.:

Cov.:

AF XY:

0.0000674

AC XY:

AN XY:

726904

show subpopulations

African (AFR)

AF:

0.00284

AC:

AN:

33480

American (AMR)

AF:

0.000246

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52798

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000629

AC:

AN:

1112004

Other (OTH)

AF:

0.000364

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000835

AC:

127

AN:

152178

Hom.:

Cov.:

AF XY:

0.000779

AC XY:

AN XY:

74408

show subpopulations

African (AFR)

AF:

0.00260

AC:

108

AN:

41514

American (AMR)

AF:

0.000654

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5156

South Asian (SAS)

AF:

0.00

AC:

AN:

4806

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000882

AC:

AN:

67998

Other (OTH)

AF:

0.00142

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000401

Hom.:

Bravo

AF:

0.00133

ESP6500AA

AF:

0.00363

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000305

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

Primary ciliary dyskinesia (3)

not specified (2)

Primary ciliary dyskinesia 9 (2)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.33

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.063

Eigen

Uncertain

0.27

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Uncertain

0.85

LIST_S2

Uncertain

0.93

M_CAP

Benign

0.032

MetaRNN

Benign

0.014

MetaSVM

Benign

-0.87

MutationAssessor

Benign

0.90

PhyloP100

4.3

PrimateAI

Uncertain

0.63

PROVEAN

Benign

-0.58

REVEL

Uncertain

0.35

Sift

Benign

0.063

Sift4G

Uncertain

0.019

Polyphen

0.94

Vest4

0.48

MVP

0.78

MPC

0.45

ClinPred

0.051

GERP RS

4.0

Varity_R

0.076

gMVP

0.12

Mutation Taster

=80/20

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over