chr2-181901786-G-C

Position:

• chr2-181901786-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001130445.3(ITPRID2):​c.733G>C​(p.Val245Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ITPRID2 NM_001130445.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.35

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITPRID2	NM_001130445.3	c.733G>C	p.Val245Leu	missense_variant	8/18	ENST00000431877.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITPRID2	ENST00000431877.7	c.733G>C	p.Val245Leu	missense_variant	8/18	1	NM_001130445.3	P3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 29, 2023

The c.733G>C (p.V245L) alteration is located in exon 8 (coding exon 8) of the SSFA2 gene. This alteration results from a G to C substitution at nucleotide position 733, causing the valine (V) at amino acid position 245 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.090
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.30	T;.;T
Eigen	Pathogenic	0.89
Eigen_PC	Pathogenic	0.86
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.83	T;T;T
M_CAP	Benign	0.032	D
MetaRNN	Uncertain	0.61	D;D;D
MetaSVM	Benign	-0.81	T
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-1.8	N;N;N
REVEL	Uncertain	0.37
Sift	Uncertain	0.0040	D;D;D
Sift4G	Uncertain	0.055	T;D;T
Polyphen		1.0	D;D;D
Vest4		0.74
MutPred		0.31		Loss of catalytic residue at Q242 (P = 0.1022);Loss of catalytic residue at Q242 (P = 0.1022);Loss of catalytic residue at Q242 (P = 0.1022);
MVP		0.40
MPC		0.19
ClinPred		0.93	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.22
gMVP		0.75

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-182766513;