7-100170469-C-T

Variant names:

• chr7-100170469-C-T
• rs779561514
• NM_152742.3:c.1501G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_152742.3(GPC2):​c.1501G>A​(p.Gly501Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000029 in 1,379,198 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000029 (0 hom.)
• Consequence: GPC2 NM_152742.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.98
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.41123667).

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.1501G>A	p.Gly501Ser	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.1501G>A	p.Gly501Ser	missense	Exon 10 of 10	ENSP00000292377.2	Q8N158
	GPC2	ENST00000893618.1		c.1483G>A	p.Gly495Ser	missense	Exon 10 of 10	ENSP00000563677.1
	GPC2	ENST00000919185.1		c.1354G>A	p.Gly452Ser	missense	Exon 9 of 9	ENSP00000589244.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.0000108 AC: 2 AN: 184824 AF XY: 0.00000998

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000671

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000290 AC: 4 AN: 1379198 Hom.: 0 Cov.: 32 AF XY: 0.00000442 AC XY: 3 AN XY: 678324

African (AFR) AF: 0.00 AC: 0 AN: 30840

American (AMR) AF: 0.00 AC: 0 AN: 34456

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21908

East Asian (EAS) AF: 0.0000271 AC: 1 AN: 36962

South Asian (SAS) AF: 0.00 AC: 0 AN: 73836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51304

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5474

European-Non Finnish (NFE) AF: 0.00000281 AC: 3 AN: 1067638

Other (OTH) AF: 0.00 AC: 0 AN: 56780

GnomAD4 genome Cov.: 31

Alfa AF: 0.0000615 Hom.: 0

ExAC AF: 0.00000824 AC: 1

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	0.13
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.21
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.31	T
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.78	T
M_CAP	Uncertain	0.26	D
MetaRNN	Benign	0.41	T
MetaSVM	Uncertain	0.28	D
MutationAssessor	Uncertain	2.7	M
PhyloP100		2.0
PrimateAI	Uncertain	0.70	T
PROVEAN	Pathogenic	-5.4	D
REVEL	Uncertain	0.56
Sift	Benign	0.054	T
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.32
MVP		0.64
MPC		0.14
ClinPred		0.92	D
GERP RS		3.6
Varity_R		0.47
gMVP		0.48
Mutation Taster		=73/27	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: rs779561514; hg19: chr7-99768092;