7-100170405-C-A

Variant names:

• chr7-100170405-C-A
• rs769690785
• NM_152742.3:c.1565G>T

Variant summary

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

The NM_152742.3(GPC2):​c.1565G>T​(p.Arg522Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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. R522Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GPC2 NM_152742.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.857
• 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: 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=0.33403647).

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.1565G>T	p.Arg522Leu	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.1565G>T	p.Arg522Leu	missense	Exon 10 of 10	ENSP00000292377.2	Q8N158
	GPC2	ENST00000893618.1		c.1547G>T	p.Arg516Leu	missense	Exon 10 of 10	ENSP00000563677.1
	GPC2	ENST00000919185.1		c.1418G>T	p.Arg473Leu	missense	Exon 9 of 9	ENSP00000589244.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1458108 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 725176

African (AFR) AF: 0.00 AC: 0 AN: 33392

American (AMR) AF: 0.00 AC: 0 AN: 44384

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25974

East Asian (EAS) AF: 0.00 AC: 0 AN: 39520

South Asian (SAS) AF: 0.00 AC: 0 AN: 85520

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53236

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5750

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110150

Other (OTH) AF: 0.00 AC: 0 AN: 60182

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.069	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.29	T
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.55	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.33	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		0.86
PrimateAI	Uncertain	0.61	T
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.19
Sift	Benign	0.20	T
Sift4G	Uncertain	0.018	D
Polyphen		0.99	D
Vest4		0.25
MutPred		0.47		Loss of methylation at R522 (P = 0.0286)
MVP		0.35
MPC		0.024
ClinPred		0.97	D
GERP RS		4.5
Varity_R		0.21
gMVP		0.33
Mutation Taster		=76/24	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: rs769690785; hg19: chr7-99768028; COSMIC: COSV52784751; COSMIC: COSV52784751;