7-100171617-G-C

Variant names:

• chr7-100171617-G-C
• rs1562957114
• NM_152742.3:c.1232C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_152742.3(GPC2):​c.1232C>G​(p.Thr411Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000723 in 1,382,692 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. T411M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: GPC2 NM_152742.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.60
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.1232C>G	p.Thr411Arg	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.1232C>G	p.Thr411Arg	missense	Exon 8 of 10	ENSP00000292377.2	Q8N158
	GPC2	ENST00000893618.1		c.1214C>G	p.Thr405Arg	missense	Exon 8 of 10	ENSP00000563677.1
	GPC2	ENST00000919185.1		c.1085C>G	p.Thr362Arg	missense	Exon 7 of 9	ENSP00000589244.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.23e-7 AC: 1 AN: 1382692 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 685468

African (AFR) AF: 0.00 AC: 0 AN: 28746

American (AMR) AF: 0.00 AC: 0 AN: 36088

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24372

East Asian (EAS) AF: 0.00 AC: 0 AN: 33268

South Asian (SAS) AF: 0.00 AC: 0 AN: 78266

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34822

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4052

European-Non Finnish (NFE) AF: 9.21e-7 AC: 1 AN: 1085704

Other (OTH) AF: 0.00 AC: 0 AN: 57374

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Uncertain	0.061	T
BayesDel_noAF	Benign	-0.15
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.32	T
Eigen	Benign	0.13
Eigen_PC	Benign	0.069
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.48	T
M_CAP	Pathogenic	0.61	D
MetaRNN	Uncertain	0.70	D
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	2.0	M
PhyloP100		2.6
PrimateAI	Pathogenic	0.81	D
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.28
Sift	Uncertain	0.019	D
Sift4G	Uncertain	0.018	D
Polyphen		0.97	D
Vest4		0.54
MutPred		0.64		Gain of MoRF binding (P = 0.0245)
MVP		0.43
MPC		2.2
ClinPred		0.96	D
GERP RS		4.3
Varity_R		0.44
gMVP		0.65
Mutation Taster		=51/49	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: rs1562957114; hg19: chr7-99769240;