rs554424170

Variant names:

• chr2-181901864-A-G
• rs554424170
• NM_001130445.3:c.811A>G

Your query was ambiguous. Multiple possible variants found:

• chr2-181901864-A-G
• chr2-181901864-A-C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001130445.3(ITPRID2):​c.811A>G​(p.Met271Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000291 in 1,613,942 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000030 (0 hom.)
• Consequence: ITPRID2 NM_001130445.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.245
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.018593162).

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.811A>G	p.Met271Val	missense	Exon 8 of 18	NP_001123917.1	P28290-1
	ITPRID2	NM_006751.7		c.811A>G	p.Met271Val	missense	Exon 8 of 17	NP_006742.2
	ITPRID2	NM_001287503.2		c.811A>G	p.Met271Val	missense	Exon 8 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.811A>G	p.Met271Val	missense	Exon 8 of 18	ENSP00000388731.2	P28290-1
	ITPRID2	ENST00000320370.11	TSL:1	c.811A>G	p.Met271Val	missense	Exon 8 of 17	ENSP00000314669.7	P28290-3
	ITPRID2	ENST00000409001.5	TSL:1	c.811A>G	p.Met271Val	missense	Exon 8 of 17	ENSP00000387319.1	E9PHV5

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152198 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000438 AC: 11 AN: 251264 AF XY: 0.0000589

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000352

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.0000301 AC: 44 AN: 1461626 Hom.: 0 Cov.: 31 AF XY: 0.0000344 AC XY: 25 AN XY: 727106

African (AFR) AF: 0.00 AC: 0 AN: 33460

American (AMR) AF: 0.0000224 AC: 1 AN: 44688

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39684

South Asian (SAS) AF: 0.000278 AC: 24 AN: 86246

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53414

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5766

European-Non Finnish (NFE) AF: 0.0000108 AC: 12 AN: 1111850

Other (OTH) AF: 0.0000828 AC: 5 AN: 60392

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152316 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74464

African (AFR) AF: 0.0000241 AC: 1 AN: 41576

American (AMR) AF: 0.00 AC: 0 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68034

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.0000312 Hom.: 0

ExAC AF: 0.0000412 AC: 5

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	0.057
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	9.2
DANN	Benign	0.89
DEOGEN2	Benign	0.087	T
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.60
FATHMM_MKL	Benign	0.71	D
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.0029	T
MetaRNN	Benign	0.019	T
MetaSVM	Benign	-0.95	T
PhyloP100		0.24
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.85	N
REVEL	Benign	0.10
Sift	Benign	0.38	T
Sift4G	Benign	0.079	T
Polyphen		0.018	B
Vest4		0.15
MutPred		0.15		Gain of sheet (P = 0.1208)
MVP		0.15
MPC		0.023
ClinPred		0.012	T
GERP RS		-3.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.019
gMVP		0.28
Mutation Taster		=98/2	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: rs554424170; hg19: chr2-182766591;