Genetic Variant GPRIN2:p.Gly237Ala (chr10-46550027-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001385282.1(GPRIN2):c.710G>C(p.Gly237Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000128 in 1,566,148 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 8/11 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000080 ( 0 hom., cov: 72)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

GPRIN2
NM_001385282.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.321

Variant links:

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]

GPRIN2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0585576).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPRIN2	NM_001385282.1 link	c.710G>C	p.Gly237Ala	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 link	c.710G>C	p.Gly237Ala	missense_variant	Exon 3 of 3	6	NM_001385282.1	ENSP00000363433.4		O60269
GPRIN2	ENST00000374317.2 link	c.710G>C	p.Gly237Ala	missense_variant	Exon 3 of 3	3		ENSP00000363436.1		O60269

Frequencies

GnomAD3 genomes

AF:

0.00000800

AC:

AN:

125052

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000175

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000801

AC:

AN:

124856

Hom.:

AF XY:

0.0000150

AC XY:

AN XY:

66830

show subpopulations

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000169

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.94e-7

AC:

AN:

1441096

Hom.:

Cov.:

111

AF XY:

0.00000139

AC XY:

AN XY:

717210

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.11e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000800

AC:

AN:

125052

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

60462

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000175

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 11, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.710G>C (p.G237A) alteration is located in exon 3 (coding exon 1) of the GPRIN2 gene. This alteration results from a G to C substitution at nucleotide position 710, causing the glycine (G) at amino acid position 237 to be replaced by an alanine (A). 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

0.092

BayesDel_noAF

Benign

-0.98

CADD

Benign

0.56

DANN

Benign

0.088

DEOGEN2

Benign

0.0064

T;T

LIST_S2

Benign

0.49

.;T

MetaRNN

Benign

0.059

T;T

PROVEAN

Benign

0.090

N;N

Sift

Benign

0.40

T;T

Sift4G

Benign

0.89

T;T

Vest4

0.15

gMVP

0.17

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over