7-100171344-C-G

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_152742.3(GPC2):​c.1403G>C​(p.Arg468Pro) 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 pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R468Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

GPC2
NM_152742.3 missense

Scores

6
10
3

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.43
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.949

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GPC2NM_152742.3 linkc.1403G>C p.Arg468Pro missense_variant Exon 9 of 10 ENST00000292377.4 NP_689955.1 Q8N158

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GPC2ENST00000292377.4 linkc.1403G>C p.Arg468Pro missense_variant Exon 9 of 10 1 NM_152742.3 ENSP00000292377.2 Q8N158
GPC2ENST00000486702.1 linkn.512G>C non_coding_transcript_exon_variant Exon 4 of 4 3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000704
AC:
1
AN:
142058
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
77128
show subpopulations
Gnomad AFR exome
AF:
0.000156
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Cov.:
33
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.00000892
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.64
BayesDel_addAF
Uncertain
0.15
D
BayesDel_noAF
Uncertain
-0.030
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.50
D
Eigen
Uncertain
0.46
Eigen_PC
Uncertain
0.34
FATHMM_MKL
Uncertain
0.90
D
LIST_S2
Benign
0.64
T
M_CAP
Pathogenic
0.62
D
MetaRNN
Pathogenic
0.95
D
MetaSVM
Benign
-0.37
T
MutationAssessor
Uncertain
2.6
M
PrimateAI
Pathogenic
0.82
D
PROVEAN
Pathogenic
-5.8
D
REVEL
Uncertain
0.49
Sift
Uncertain
0.0040
D
Sift4G
Pathogenic
0.0
D
Polyphen
1.0
D
Vest4
0.76
MutPred
0.76
Loss of MoRF binding (P = 0.0061);
MVP
0.28
MPC
2.6
ClinPred
0.99
D
GERP RS
4.3
Varity_R
0.92
gMVP
0.83

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: rs202046333; hg19: chr7-99768967; API