rs2303554

Variant names:

• chr2-181928257-T-A
• rs2303554
• NM_001130445.3:c.3772T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001130445.3(ITPRID2):​c.3772T>A​(p.Tyr1258Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0367 in 1,537,738 control chromosomes in the GnomAD database, including 1,890 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.059 (409 hom., cov: 32)
  • Exomes 𝑓: 0.034 (1481 hom.)
• Consequence: ITPRID2 NM_001130445.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.89
• Publications: 13 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0014821291).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.117 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITPRID2	NM_001130445.3	c.3772T>A	p.Tyr1258Asn	missense_variant	Exon 17 of 18	ENST00000431877.7	NP_001123917.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITPRID2	ENST00000431877.7	c.3772T>A	p.Tyr1258Asn	missense_variant	Exon 17 of 18	1	NM_001130445.3	ENSP00000388731.2

Frequencies

GnomAD3 genomes AF: 0.0591 AC: 8994 AN: 152138 Hom.: 400 Cov.: 32

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.132

Gnomad AMR AF: 0.0329

Gnomad ASJ AF: 0.0332

Gnomad EAS AF: 0.0970

Gnomad SAS AF: 0.0999

Gnomad FIN AF: 0.0326

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0277

Gnomad OTH AF: 0.0540

GnomAD2 exomes AF: 0.0458 AC: 6616 AN: 144610 AF XY: 0.0478

Gnomad AFR exome AF: 0.120

Gnomad AMR exome AF: 0.0207

Gnomad ASJ exome AF: 0.0335

Gnomad EAS exome AF: 0.0967

Gnomad FIN exome AF: 0.0350

Gnomad NFE exome AF: 0.0277

Gnomad OTH exome AF: 0.0355

GnomAD4 exome AF: 0.0342 AC: 47368 AN: 1385482 Hom.: 1481 Cov.: 28 AF XY: 0.0355 AC XY: 24280 AN XY: 683142

African (AFR) AF: 0.126 AC: 3859 AN: 30740

American (AMR) AF: 0.0214 AC: 698 AN: 32688

Ashkenazi Jewish (ASJ) AF: 0.0334 AC: 824 AN: 24706

East Asian (EAS) AF: 0.126 AC: 4484 AN: 35542

South Asian (SAS) AF: 0.0930 AC: 7052 AN: 75864

European-Finnish (FIN) AF: 0.0342 AC: 1680 AN: 49156

Middle Eastern (MID) AF: 0.0557 AC: 313 AN: 5624

European-Non Finnish (NFE) AF: 0.0242 AC: 25993 AN: 1073716

Other (OTH) AF: 0.0429 AC: 2465 AN: 57446

GnomAD4 genome AF: 0.0594 AC: 9037 AN: 152256 Hom.: 409 Cov.: 32 AF XY: 0.0606 AC XY: 4512 AN XY: 74468

African (AFR) AF: 0.119 AC: 4962 AN: 41534

American (AMR) AF: 0.0329 AC: 503 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0332 AC: 115 AN: 3468

East Asian (EAS) AF: 0.0972 AC: 504 AN: 5184

South Asian (SAS) AF: 0.100 AC: 482 AN: 4820

European-Finnish (FIN) AF: 0.0326 AC: 346 AN: 10614

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0277 AC: 1883 AN: 68022

Other (OTH) AF: 0.0543 AC: 115 AN: 2116

Alfa AF: 0.0342 Hom.: 111

Bravo AF: 0.0606

TwinsUK AF: 0.0256 AC: 95

ALSPAC AF: 0.0270 AC: 104

ExAC AF: 0.0574 AC: 1398

Asia WGS AF: 0.108 AC: 374 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.038
BayesDel_addAF	Benign	-0.75	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	15
DANN	Benign	0.70
DEOGEN2	Benign	0.020	T;T;.
Eigen	Benign	-0.82
Eigen_PC	Benign	-0.65
FATHMM_MKL	Benign	0.056	N
LIST_S2	Benign	0.45	T;T;T
MetaRNN	Benign	0.0015	T;T;T
MetaSVM	Benign	-0.95	T
PhyloP100		1.9
PROVEAN	Benign	0.54	N;N;N
REVEL	Benign	0.092
Sift	Benign	0.60	T;T;T
Sift4G	Benign	0.43	T;T;T
Polyphen		0.0	B;B;B
Vest4		0.066
MPC		0.028
ClinPred		0.0049	T
GERP RS		4.8
Varity_R		0.034
gMVP		0.077
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2303554; hg19: chr2-182792984; COSMIC: COSV57469369;