chr7-100171543-C-T

Variant names:

• chr7-100171543-C-T
• NM_152742.3:c.1306G>A

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.1306G>A​(p.Gly436Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000154 in 1,294,534 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: GPC2 NM_152742.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.82
• 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=0.24764049).

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.1306G>A	p.Gly436Ser	missense	Exon 8 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.1306G>A	p.Gly436Ser	missense	Exon 8 of 10	ENSP00000292377.2	Q8N158
	GPC2	ENST00000893618.1		c.1288G>A	p.Gly430Ser	missense	Exon 8 of 10	ENSP00000563677.1
	GPC2	ENST00000919185.1		c.1159G>A	p.Gly387Ser	missense	Exon 7 of 9	ENSP00000589244.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000154 AC: 2 AN: 1294534 Hom.: 0 Cov.: 33 AF XY: 0.00000157 AC XY: 1 AN XY: 637256

African (AFR) AF: 0.00 AC: 0 AN: 26326

American (AMR) AF: 0.00 AC: 0 AN: 21568

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21730

East Asian (EAS) AF: 0.00 AC: 0 AN: 28142

South Asian (SAS) AF: 0.00 AC: 0 AN: 68214

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32492

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3810

European-Non Finnish (NFE) AF: 0.00000193 AC: 2 AN: 1038852

Other (OTH) AF: 0.00 AC: 0 AN: 53400

GnomAD4 genome Cov.: 32

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	0.18
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	22
DANN	Benign	0.97
DEOGEN2	Benign	0.30	T
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.28
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.68	T
M_CAP	Pathogenic	0.45	D
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L
PhyloP100		1.8
PrimateAI	Pathogenic	0.79	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.075
Sift	Benign	0.41	T
Sift4G	Benign	0.12	T
Polyphen		0.29	B
Vest4		0.26
MutPred		0.59		Gain of glycosylation at G436 (P = 0.0448)
MVP		0.11
MPC		1.3
ClinPred		0.78	D
GERP RS		3.5
Varity_R		0.21
gMVP		0.57
Mutation Taster		=56/44	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

hg19: chr7-99769166;