NM_152742.3:c.1550T>G

Variant names:

• chr7-100170420-A-C
• rs760655243
• NM_152742.3:c.1550T>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_152742.3(GPC2):​c.1550T>G​(p.Val517Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000168 in 1,607,372 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000018 (0 hom.)
• Consequence: GPC2 NM_152742.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.886
• Publications: 1 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: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06439999).
• BP6: Variant 7-100170420-A-C is Benign according to our data. Variant chr7-100170420-A-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2386392.Status of the report is criteria_provided_single_submitter, 1 stars.

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.1550T>G	p.Val517Gly	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.1550T>G	p.Val517Gly	missense	Exon 10 of 10	ENSP00000292377.2	Q8N158
	GPC2	ENST00000893618.1		c.1532T>G	p.Val511Gly	missense	Exon 10 of 10	ENSP00000563677.1
	GPC2	ENST00000919185.1		c.1403T>G	p.Val468Gly	missense	Exon 9 of 9	ENSP00000589244.1

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 151978 Hom.: 0 Cov.: 31

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000124 AC: 3 AN: 242710 AF XY: 0.00000758

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000901

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000179 AC: 26 AN: 1455394 Hom.: 0 Cov.: 32 AF XY: 0.0000124 AC XY: 9 AN XY: 723718

African (AFR) AF: 0.0000600 AC: 2 AN: 33360

American (AMR) AF: 0.0000680 AC: 3 AN: 44148

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25838

East Asian (EAS) AF: 0.00 AC: 0 AN: 39420

South Asian (SAS) AF: 0.00 AC: 0 AN: 85160

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53250

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5748

European-Non Finnish (NFE) AF: 0.0000171 AC: 19 AN: 1108394

Other (OTH) AF: 0.0000166 AC: 1 AN: 60076

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 151978 Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1 AN XY: 74220

African (AFR) AF: 0.00 AC: 0 AN: 41366

American (AMR) AF: 0.00 AC: 0 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10594

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67980

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.0000165 AC: 2

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.10
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	8.3
DANN	Benign	0.70
DEOGEN2	Benign	0.15	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.12	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.064	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.77	N
PhyloP100		0.89
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.061
Sift	Benign	0.35	T
Sift4G	Uncertain	0.016	D
Polyphen		0.0	B
Vest4		0.11
MutPred		0.32		Loss of stability (P = 0.0887)
MVP		0.10
MPC		0.018
ClinPred		0.020	T
GERP RS		2.1
Varity_R		0.087
gMVP		0.23
Mutation Taster		=83/17	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: rs760655243; hg19: chr7-99768043; COSMIC: COSV52784028; COSMIC: COSV52784028;