Genetic Variant ITPRID2:p.Ala20Thr (chr2-181892124-G-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001130445.3(ITPRID2):c.58G>A(p.Ala20Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000475 in 1,558,702 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000046 ( 0 hom. )

Consequence

ITPRID2
NM_001130445.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.19

Publications

0 publications found

Variant links:

Genes affected

ITPRID2 (HGNC:11319): (ITPR interacting domain containing 2) Enables actin filament binding activity. Located in cytosol; nucleoplasm; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ITPRID2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.051273346).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001130445.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ITPRID2	NM_001130445.3	MANE Select	c.58G>A	p.Ala20Thr	missense	Exon 1 of 18	NP_001123917.1	P28290-1
ITPRID2	NM_006751.7		c.58G>A	p.Ala20Thr	missense	Exon 1 of 17	NP_006742.2
ITPRID2	NM_001287503.2		c.58G>A	p.Ala20Thr	missense	Exon 1 of 17	NP_001274432.1	E9PHV5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ITPRID2	ENST00000431877.7	TSL:1 MANE Select	c.58G>A	p.Ala20Thr	missense	Exon 1 of 18	ENSP00000388731.2	P28290-1
ITPRID2	ENST00000320370.11	TSL:1	c.58G>A	p.Ala20Thr	missense	Exon 1 of 17	ENSP00000314669.7	P28290-3
ITPRID2	ENST00000409001.5	TSL:1	c.58G>A	p.Ala20Thr	missense	Exon 1 of 17	ENSP00000387319.1	E9PHV5

Frequencies

GnomAD3 genomes

AF:

0.0000591

AC:

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00186

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000106

AC:

AN:

160324

AF XY:

0.000153

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000462

AC:

AN:

1406378

Hom.:

Cov.:

AF XY:

0.0000619

AC XY:

AN XY:

694366

show subpopulations

African (AFR)

AF:

0.0000312

AC:

AN:

32064

American (AMR)

AF:

0.00

AC:

AN:

36734

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25246

East Asian (EAS)

AF:

0.00

AC:

AN:

36510

South Asian (SAS)

AF:

0.000778

AC:

AN:

79738

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48978

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4882

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1083948

Other (OTH)

AF:

0.0000343

AC:

AN:

58278

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

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:

0.0000591

AC:

AN:

152324

Hom.:

Cov.:

AF XY:

0.000107

AC XY:

AN XY:

74488

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41590

American (AMR)

AF:

0.00

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5162

South Asian (SAS)

AF:

0.00186

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68012

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.531

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:

0.00

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.000106

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.85

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.35

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

Eigen

Uncertain

0.50

Eigen_PC

Uncertain

0.43

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.93

M_CAP

Uncertain

0.15

MetaRNN

Benign

0.051

MetaSVM

Benign

-0.99

PhyloP100

4.2

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

-0.63

REVEL

Benign

0.10

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.49

MutPred

0.23

Gain of phosphorylation at A20 (P = 0.0373)

MVP

0.19

MPC

2.0

ClinPred

0.24

GERP RS

3.5

PromoterAI

0.34

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.39

gMVP

0.49

Mutation Taster

=92/8

polymorphism

(source)

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

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