7-100171408-G-A

Variant names:

• chr7-100171408-G-A
• rs1347182058
• NM_152742.3:c.1339C>T

Variant summary

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

The NM_152742.3(GPC2):​c.1339C>T​(p.Pro447Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000375 in 1,333,436 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign 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. P447A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000037 (0 hom.)
• Consequence: GPC2 NM_152742.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.312
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.057729304).

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.1339C>T	p.Pro447Ser	missense	Exon 9 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.1339C>T	p.Pro447Ser	missense	Exon 9 of 10	ENSP00000292377.2	Q8N158
	GPC2	ENST00000893618.1		c.1321C>T	p.Pro441Ser	missense	Exon 9 of 10	ENSP00000563677.1
	GPC2	ENST00000919185.1		c.1192C>T	p.Pro398Ser	missense	Exon 8 of 9	ENSP00000589244.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000375 AC: 5 AN: 1333436 Hom.: 0 Cov.: 33 AF XY: 0.00000458 AC XY: 3 AN XY: 654880

African (AFR) AF: 0.0000371 AC: 1 AN: 26918

American (AMR) AF: 0.00 AC: 0 AN: 28190

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20806

East Asian (EAS) AF: 0.00 AC: 0 AN: 30578

South Asian (SAS) AF: 0.00 AC: 0 AN: 70808

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45096

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5006

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1051246

Other (OTH) AF: 0.0000730 AC: 4 AN: 54788

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	9.7
DANN	Benign	0.92
DEOGEN2	Benign	0.10	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.066	N
LIST_S2	Benign	0.30	T
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.058	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.76	N
PhyloP100		0.31
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-0.14	N
REVEL	Benign	0.023
Sift	Uncertain	0.0040	D
Sift4G	Benign	0.086	T
Polyphen		0.042	B
Vest4		0.091
MutPred		0.36		Gain of phosphorylation at P447 (P = 0.0704)
MVP		0.014
MPC		1.2
ClinPred		0.092	T
GERP RS		-2.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.094
gMVP		0.32
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs1347182058; hg19: chr7-99769031;