2-181898883-A-C

Variant names:

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

Variant summary

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

The NM_001130445.3(ITPRID2):​c.368A>C​(p.Asn123Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N123S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ITPRID2 NM_001130445.3 missense
• Clinical Significance: Not reported in ClinVar
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.33562943).

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>C	p.Asn123Thr	missense	Exon 5 of 18	NP_001123917.1	P28290-1
	ITPRID2	NM_006751.7		c.368A>C	p.Asn123Thr	missense	Exon 5 of 17	NP_006742.2
	ITPRID2	NM_001287503.2		c.368A>C	p.Asn123Thr	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>C	p.Asn123Thr	missense	Exon 5 of 18	ENSP00000388731.2	P28290-1
	ITPRID2	ENST00000320370.11	TSL:1	c.368A>C	p.Asn123Thr	missense	Exon 5 of 17	ENSP00000314669.7	P28290-3
	ITPRID2	ENST00000409001.5	TSL:1	c.368A>C	p.Asn123Thr	missense	Exon 5 of 17	ENSP00000387319.1	E9PHV5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.12	T
Eigen	Uncertain	0.65
Eigen_PC	Pathogenic	0.66
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.85	D
M_CAP	Benign	0.0069	T
MetaRNN	Benign	0.34	T
MetaSVM	Benign	-1.1	T
PhyloP100		6.4
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-0.67	N
REVEL	Benign	0.16
Sift	Benign	0.14	T
Sift4G	Benign	0.089	T
Polyphen		1.0	D
Vest4		0.48
MutPred		0.16		Gain of glycosylation at N123 (P = 0.047)
MVP		0.26
MPC		2.0
ClinPred		0.83	D
GERP RS		5.8
Varity_R		0.093
gMVP		0.36
Mutation Taster		=233/67	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: rs1227561673; hg19: chr2-182763610;