10-46549412-T-C

Variant names:

• chr10-46549412-T-C
• rs782294590
• NM_001385282.1:c.1325A>G

Variant summary

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

The NM_001385282.1(GPRIN2):​c.1325A>G​(p.Gln442Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000428 in 1,401,852 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 79)
  • Exomes 𝑓: 0.0000043 (0 hom.)
• Consequence: GPRIN2 NM_001385282.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.07

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=0.20782596).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPRIN2	NM_001385282.1	c.1325A>G	p.Gln442Arg	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.1325A>G	p.Gln442Arg	missense_variant	Exon 3 of 3	6	NM_001385282.1	ENSP00000363433.4
GPRIN2	ENST00000374317.2	c.1325A>G	p.Gln442Arg	missense_variant	Exon 3 of 3	3		ENSP00000363436.1

Frequencies

GnomAD3 genomes Cov.: 79

GnomAD4 exome AF: 0.00000428 AC: 6 AN: 1401852 Hom.: 0 Cov.: 102 AF XY: 0.00000289 AC XY: 2 AN XY: 691902

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000107

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000184

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 79

Alfa AF: 0.0000843 Hom.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 20, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1325A>G (p.Q442R) alteration is located in exon 3 (coding exon 1) of the GPRIN2 gene. This alteration results from a A to G substitution at nucleotide position 1325, causing the glutamine (Q) at amino acid position 442 to be replaced by an arginine (R). 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	0.11
BayesDel_noAF	Benign	-0.42
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.025	T;T
LIST_S2	Benign	0.58	.;T
MetaRNN	Benign	0.21	T;T
PROVEAN	Uncertain	-3.0	D;D
Sift	Benign	0.11	T;T
Sift4G	Benign	0.53	T;T
Vest4		0.24
gMVP		0.85

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: rs782294590; hg19: chr10-47000205;