7-100170385-G-A

Variant names:

• chr7-100170385-G-A
• rs776706956
• NM_152742.3:c.1585C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152742.3(GPC2):​c.1585C>T​(p.Pro529Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000186 in 1,612,374 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 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: 0.000017 (0 hom.)
• Consequence: GPC2 NM_152742.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.57
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14221606).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152742.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPC2	NM_152742.3	MANE Select	c.1585C>T	p.Pro529Ser	missense	Exon 10 of 10	NP_689955.1	Q8N158

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPC2	ENST00000292377.4	TSL:1 MANE Select	c.1585C>T	p.Pro529Ser	missense	Exon 10 of 10	ENSP00000292377.2	Q8N158
	GPC2	ENST00000893618.1		c.1567C>T	p.Pro523Ser	missense	Exon 10 of 10	ENSP00000563677.1
	GPC2	ENST00000919185.1		c.1438C>T	p.Pro480Ser	missense	Exon 9 of 9	ENSP00000589244.1

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 152010 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000197

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000495 AC: 12 AN: 242360 AF XY: 0.0000228

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000613

Gnomad ASJ exome AF: 0.000926

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000171

GnomAD4 exome AF: 0.0000171 AC: 25 AN: 1460364 Hom.: 0 Cov.: 32 AF XY: 0.0000110 AC XY: 8 AN XY: 726410

African (AFR) AF: 0.00 AC: 0 AN: 33432

American (AMR) AF: 0.0000449 AC: 2 AN: 44590

Ashkenazi Jewish (ASJ) AF: 0.000691 AC: 18 AN: 26064

East Asian (EAS) AF: 0.00 AC: 0 AN: 39620

South Asian (SAS) AF: 0.00 AC: 0 AN: 85922

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53350

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111290

Other (OTH) AF: 0.0000331 AC: 2 AN: 60334

GnomAD4 genome AF: 0.0000329 AC: 5 AN: 152010 Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1 AN XY: 74250

African (AFR) AF: 0.00 AC: 0 AN: 41394

American (AMR) AF: 0.000197 AC: 3 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67960

Other (OTH) AF: 0.00 AC: 0 AN: 2084

Alfa AF: 0.0000868 Hom.: 0

Bravo AF: 0.0000453

ExAC AF: 0.0000412 AC: 5

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T
Eigen	Benign	0.077
Eigen_PC	Benign	-0.025
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		2.6
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.18
Sift	Benign	0.19	T
Sift4G	Benign	0.26	T
Polyphen		1.0	D
Vest4		0.18
MutPred		0.46		Gain of phosphorylation at P529 (P = 0.0011)
MVP		0.21
MPC		0.14
ClinPred		0.29	T
GERP RS		1.9
Varity_R		0.063
gMVP		0.37
Mutation Taster		=92/8	polymorphism

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

Other links and lift over

dbSNP: rs776706956; hg19: chr7-99768008;