chr10-46550082-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001385282.1(GPRIN2):​c.655G>A​(p.Glu219Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,092 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 7/11 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 73)
Exomes 𝑓: 0.0000034 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

GPRIN2
NM_001385282.1 missense

Scores

1
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.879
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.08089438).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GPRIN2NM_001385282.1 linkc.655G>A p.Glu219Lys missense_variant Exon 3 of 3 ENST00000374314.6 NP_001372211.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GPRIN2ENST00000374314.6 linkc.655G>A p.Glu219Lys missense_variant Exon 3 of 3 6 NM_001385282.1 ENSP00000363433.4 O60269
GPRIN2ENST00000374317.2 linkc.655G>A p.Glu219Lys missense_variant Exon 3 of 3 3 ENSP00000363436.1 O60269

Frequencies

GnomAD3 genomes
AF:
0.00
AC:
2
AN:
152310
Hom.:
0
Cov.:
73
FAILED QC
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000384
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000342
AC:
5
AN:
1461092
Hom.:
0
Cov.:
124
AF XY:
0.00000413
AC XY:
3
AN XY:
726836
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000756
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.0000131
AC:
2
AN:
152310
Hom.:
0
Cov.:
73
AF XY:
0.0000134
AC XY:
1
AN XY:
74418
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000384
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
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
Jun 07, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.655G>A (p.E219K) alteration is located in exon 3 (coding exon 1) of the GPRIN2 gene. This alteration results from a G to A substitution at nucleotide position 655, causing the glutamic acid (E) at amino acid position 219 to be replaced by a lysine (K). 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
0.071
BayesDel_noAF
Pathogenic
0.27
CADD
Benign
16
DANN
Benign
0.91
DEOGEN2
Benign
0.0018
T;T
LIST_S2
Benign
0.49
.;T
MetaRNN
Benign
0.081
T;T
PROVEAN
Benign
-0.43
N;N
Sift
Benign
0.18
T;T
Sift4G
Benign
0.54
T;T
Vest4
0.16
gMVP
0.33

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.

Other links and lift over

dbSNP: rs782785817; hg19: chr10-46999535; COSMIC: COSV65401239; API