10-46550084-G-A

Variant names:

• chr10-46550084-G-A
• rs1362763086
• NM_001385282.1:c.653C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001385282.1(GPRIN2):​c.653C>T​(p.Ala218Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 8/12 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 73)
• Consequence: GPRIN2 NM_001385282.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.840

Genes affected

GPRIN2 (HGNC:23730): (G protein regulated inducer of neurite outgrowth 2) Predicted to be involved in neuron projection development. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08110419).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPRIN2	NM_001385282.1	c.653C>T	p.Ala218Val	missense_variant	Exon 3 of 3	ENST00000374314.6	NP_001372211.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPRIN2	ENST00000374314.6	c.653C>T	p.Ala218Val	missense_variant	Exon 3 of 3	6	NM_001385282.1	ENSP00000363433.4
GPRIN2	ENST00000374317.2	c.653C>T	p.Ala218Val	missense_variant	Exon 3 of 3	3		ENSP00000363436.1

Frequencies

GnomAD3 genomes Cov.: 73

GnomAD4 exome Cov.: 125

GnomAD4 genome Cov.: 73

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 20, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.653C>T (p.A218V) alteration is located in exon 3 (coding exon 1) of the GPRIN2 gene. This alteration results from a C to T substitution at nucleotide position 653, causing the alanine (A) at amino acid position 218 to be replaced by a valine (V). 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	Benign	0.086
BayesDel_noAF	Benign	-0.66
CADD	Benign	8.6
DANN	Benign	0.97
DEOGEN2	Benign	0.0040	T;T
LIST_S2	Benign	0.44	.;T
MetaRNN	Benign	0.081	T;T
PROVEAN	Benign	-1.0	N;N
Sift	Benign	0.30	T;T
Sift4G	Benign	0.43	T;T
Vest4		0.11
gMVP		0.093

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

Publications

LitVar

Other links and lift over

dbSNP: rs1362763086; hg19: chr10-46999533;