chr2-181898883-A-G

Variant names:

• chr2-181898883-A-G
• rs1227561673
• NM_001130445.3:c.368A>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001130445.3(ITPRID2):​c.368A>G​(p.Asn123Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,458,232 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ITPRID2 NM_001130445.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.41
• Publications: 0 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.368A>G	p.Asn123Ser	missense	Exon 5 of 18	NP_001123917.1	P28290-1
	ITPRID2	NM_006751.7		c.368A>G	p.Asn123Ser	missense	Exon 5 of 17	NP_006742.2
	ITPRID2	NM_001287503.2		c.368A>G	p.Asn123Ser	missense	Exon 5 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.368A>G	p.Asn123Ser	missense	Exon 5 of 18	ENSP00000388731.2	P28290-1
	ITPRID2	ENST00000320370.11	TSL:1	c.368A>G	p.Asn123Ser	missense	Exon 5 of 17	ENSP00000314669.7	P28290-3
	ITPRID2	ENST00000409001.5	TSL:1	c.368A>G	p.Asn123Ser	missense	Exon 5 of 17	ENSP00000387319.1	E9PHV5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1458232 Hom.: 0 Cov.: 29 AF XY: 0.00000276 AC XY: 2 AN XY: 725668

African (AFR) AF: 0.00 AC: 0 AN: 33368

American (AMR) AF: 0.00 AC: 0 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26076

East Asian (EAS) AF: 0.00 AC: 0 AN: 39604

South Asian (SAS) AF: 0.00 AC: 0 AN: 86138

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53392

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1108960

Other (OTH) AF: 0.00 AC: 0 AN: 60232

GnomAD4 genome Cov.: 32

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	0.13
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T
Eigen	Pathogenic	0.71
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.0077	T
MetaRNN	Benign	0.32	T
MetaSVM	Benign	-1.1	T
PhyloP100		6.4
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.16
Sift	Benign	0.034	D
Sift4G	Benign	0.31	T
Polyphen		1.0	D
Vest4		0.36
MutPred		0.11		Gain of phosphorylation at N123 (P = 0.0388)
MVP		0.31
MPC		1.8
ClinPred		0.85	D
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.089
gMVP		0.27
Mutation Taster		=233/67	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.39		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.39		Position offset: 1

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

Other links and lift over

dbSNP: rs1227561673; hg19: chr2-182763610;