2-181900764-G-T

Variant names:

• chr2-181900764-G-T
• rs760424706
• NM_001130445.3:c.572G>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001130445.3(ITPRID2):​c.572G>T​(p.Arg191Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000411 in 1,460,970 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: ITPRID2 NM_001130445.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.63

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3775016).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITPRID2	NM_001130445.3	c.572G>T	p.Arg191Leu	missense_variant	Exon 7 of 18	ENST00000431877.7	NP_001123917.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITPRID2	ENST00000431877.7	c.572G>T	p.Arg191Leu	missense_variant	Exon 7 of 18	1	NM_001130445.3	ENSP00000388731.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000798 AC: 2 AN: 250768 Hom.: 0 AF XY: 0.00000738 AC XY: 1 AN XY: 135518

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 SAS 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: 0.00000411 AC: 6 AN: 1460970 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 726758

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000540

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Uncertain	0.028	T
BayesDel_noAF	Benign	-0.18
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.18	T;.;T
Eigen	Pathogenic	0.74
Eigen_PC	Pathogenic	0.74
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.76	T;T;T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.38	T;T;T
MetaSVM	Benign	-1.1	T
PrimateAI	Uncertain	0.71	T
PROVEAN	Uncertain	-2.4	N;N;N
REVEL	Benign	0.19
Sift	Uncertain	0.0080	D;D;D
Sift4G	Uncertain	0.027	D;D;D
Polyphen		1.0	D;D;D
Vest4		0.47
MutPred		0.30		Loss of disorder (P = 0.0521);Loss of disorder (P = 0.0521);Loss of disorder (P = 0.0521);
MVP		0.33
MPC		0.20
ClinPred		0.74	D
GERP RS		5.9
Varity_R		0.16
gMVP		0.60

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

Other links and lift over

dbSNP: rs760424706; hg19: chr2-182765491;