rs760424706

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr2-181900764-G-A
• chr2-181900764-G-C
• chr2-181900764-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001130445.3(ITPRID2):​c.572G>A​(p.Arg191His) variant causes a missense change. The variant allele was found at a frequency of 0.0000279 in 1,613,046 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R191C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000030 (0 hom.)
• Consequence: ITPRID2 NM_001130445.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.63
• Publications: 2 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.33563906).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITPRID2	NM_001130445.3	MANE Select	c.572G>A	p.Arg191His	missense	Exon 7 of 18	NP_001123917.1	P28290-1
	ITPRID2	NM_006751.7		c.572G>A	p.Arg191His	missense	Exon 7 of 17	NP_006742.2
	ITPRID2	NM_001287503.2		c.572G>A	p.Arg191His	missense	Exon 7 of 17	NP_001274432.1	E9PHV5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITPRID2	ENST00000431877.7	TSL:1 MANE Select	c.572G>A	p.Arg191His	missense	Exon 7 of 18	ENSP00000388731.2	P28290-1
	ITPRID2	ENST00000320370.11	TSL:1	c.572G>A	p.Arg191His	missense	Exon 7 of 17	ENSP00000314669.7	P28290-3
	ITPRID2	ENST00000409001.5	TSL:1	c.572G>A	p.Arg191His	missense	Exon 7 of 17	ENSP00000387319.1	E9PHV5

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152076 Hom.: 0 Cov.: 33

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: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000160 AC: 4 AN: 250768 AF XY: 0.0000295

Gnomad AFR exome AF: 0.0000616

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000301 AC: 44 AN: 1460970 Hom.: 0 Cov.: 31 AF XY: 0.0000344 AC XY: 25 AN XY: 726758

African (AFR) AF: 0.0000598 AC: 2 AN: 33438

American (AMR) AF: 0.00 AC: 0 AN: 44630

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26102

East Asian (EAS) AF: 0.0000253 AC: 1 AN: 39596

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86108

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53406

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.0000351 AC: 39 AN: 1111568

Other (OTH) AF: 0.00 AC: 0 AN: 60364

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152076 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74292

African (AFR) AF: 0.00 AC: 0 AN: 41424

American (AMR) AF: 0.00 AC: 0 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67980

Other (OTH) AF: 0.00 AC: 0 AN: 2084

Alfa AF: 0.0000329 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.00000824 AC: 1

EpiCase AF: 0.00

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.37
CADD	Pathogenic	31
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.16	T
Eigen	Pathogenic	0.73
Eigen_PC	Pathogenic	0.74
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.0097	T
MetaRNN	Benign	0.34	T
MetaSVM	Benign	-1.1	T
PhyloP100		4.6
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.16
Sift	Uncertain	0.027	D
Sift4G	Benign	0.062	T
Polyphen		1.0	D
Vest4		0.25
MVP		0.55
MPC		0.20
ClinPred		0.68	D
GERP RS		5.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.086
gMVP		0.45
Mutation Taster		=94/6	polymorphism

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: rs760424706; hg19: chr2-182765491;