Genetic Variant NM_152742.3:c.1736G>A (chr7-100170234-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_152742.3(GPC2):c.1736G>A(p.Arg579Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000534 in 1,553,392 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000056 ( 0 hom. )

Consequence

GPC2
NM_152742.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.16

Variant links:

Genes affected

GPC2 (HGNC:4450): (glypican 2) Predicted to be involved in several processes, including positive regulation of neuron projection development; regulation of protein localization to membrane; and smoothened signaling pathway. Located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

GPC2 links:

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=0.15478244).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPC2	NM_152742.3 link	c.1736G>A	p.Arg579Gln	missense_variant	Exon 10 of 10	ENST00000292377.4	NP_689955.1	Q8N158

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPC2	ENST00000292377.4 link	c.1736G>A	p.Arg579Gln	missense_variant	Exon 10 of 10	1	NM_152742.3	ENSP00000292377.2		Q8N158

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152060

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:

0.000415

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000372

AC:

AN:

161438

Hom.:

AF XY:

0.0000469

AC XY:

AN XY:

85222

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:

0.000173

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000316

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000557

AC:

AN:

1401214

Hom.:

Cov.:

AF XY:

0.0000564

AC XY:

AN XY:

691488

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:

0.000151

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000565

Gnomad4 OTH exome

AF:

0.0000861

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152178

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74406

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:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000416

ExAC

AF:

0.0000518

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jun 28, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1736G>A (p.R579Q) alteration is located in exon 10 (coding exon 10) of the GPC2 gene. This alteration results from a G to A substitution at nucleotide position 1736, causing the arginine (R) at amino acid position 579 to be replaced by a glutamine (Q). 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_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.32

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.15

Eigen

Uncertain

0.43

Eigen_PC

Uncertain

0.49

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.69

M_CAP

Benign

0.036

MetaRNN

Benign

0.15

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.1

PrimateAI

Benign

0.46

PROVEAN

Benign

-1.4

REVEL

Benign

0.19

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.38

MutPred

0.43

Loss of methylation at R579 (P = 0.0233);

MVP

0.29

MPC

0.14

ClinPred

0.44

GERP RS

5.3

Varity_R

0.54

gMVP

0.32

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