2-181892271-G-T

Variant names:

• chr2-181892271-G-T
• rs370480664
• NM_001130445.3:c.205G>T

Variant summary

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

The NM_001130445.3(ITPRID2):​c.205G>T​(p.Gly69*) variant causes a stop gained change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ITPRID2 NM_001130445.3 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.90
• 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.205G>T	p.Gly69*	stop_gained	Exon 1 of 18	NP_001123917.1	P28290-1
	ITPRID2	NM_006751.7		c.205G>T	p.Gly69*	stop_gained	Exon 1 of 17	NP_006742.2
	ITPRID2	NM_001287503.2		c.205G>T	p.Gly69*	stop_gained	Exon 1 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.205G>T	p.Gly69*	stop_gained	Exon 1 of 18	ENSP00000388731.2	P28290-1
	ITPRID2	ENST00000320370.11	TSL:1	c.205G>T	p.Gly69*	stop_gained	Exon 1 of 17	ENSP00000314669.7	P28290-3
	ITPRID2	ENST00000409001.5	TSL:1	c.205G>T	p.Gly69*	stop_gained	Exon 1 of 17	ENSP00000387319.1	E9PHV5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.57	D
BayesDel_noAF	Pathogenic	0.58
CADD	Pathogenic	36
DANN	Uncertain	0.99
Eigen	Pathogenic	0.81
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Uncertain	0.95	D
PhyloP100		4.9
Vest4		0.081
GERP RS		4.3
PromoterAI		0.020	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=9/191	disease causing (fs/PTC)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs370480664; hg19: chr2-182756998;