chr7-100171569-G-A

Variant names:

• chr7-100171569-G-A
• rs368040702
• NM_152742.3:c.1280C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_152742.3(GPC2):​c.1280C>T​(p.Ala427Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000767 in 1,494,862 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00045 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00080 (1 hom.)
• Consequence: GPC2 NM_152742.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.558
• 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.036485106).

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.1280C>T	p.Ala427Val	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.1280C>T	p.Ala427Val	missense	Exon 8 of 10	ENSP00000292377.2	Q8N158
	GPC2	ENST00000893618.1		c.1262C>T	p.Ala421Val	missense	Exon 8 of 10	ENSP00000563677.1
	GPC2	ENST00000919185.1		c.1133C>T	p.Ala378Val	missense	Exon 7 of 9	ENSP00000589244.1

Frequencies

GnomAD3 genomes AF: 0.000447 AC: 68 AN: 151962 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000720

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000945

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000721

Gnomad OTH AF: 0.000956

GnomAD2 exomes AF: 0.000412 AC: 43 AN: 104468 AF XY: 0.000448

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000170

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000172

Gnomad NFE exome AF: 0.000843

Gnomad OTH exome AF: 0.000368

GnomAD4 exome AF: 0.000804 AC: 1079 AN: 1342792 Hom.: 1 Cov.: 33 AF XY: 0.000755 AC XY: 501 AN XY: 663944

African (AFR) AF: 0.000180 AC: 5 AN: 27852

American (AMR) AF: 0.000276 AC: 8 AN: 29008

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23486

East Asian (EAS) AF: 0.00 AC: 0 AN: 30210

South Asian (SAS) AF: 0.00 AC: 0 AN: 73940

European-Finnish (FIN) AF: 0.000177 AC: 6 AN: 33868

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3962

European-Non Finnish (NFE) AF: 0.000977 AC: 1040 AN: 1064842

Other (OTH) AF: 0.000360 AC: 20 AN: 55624

GnomAD4 genome AF: 0.000447 AC: 68 AN: 152070 Hom.: 0 Cov.: 32 AF XY: 0.000336 AC XY: 25 AN XY: 74370

African (AFR) AF: 0.000120 AC: 5 AN: 41518

American (AMR) AF: 0.000719 AC: 11 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5160

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.0000945 AC: 1 AN: 10578

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.000721 AC: 49 AN: 67918

Other (OTH) AF: 0.000946 AC: 2 AN: 2114

Alfa AF: 0.000539 Hom.: 0

Bravo AF: 0.000510

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000326 AC: 2

ExAC AF: 0.000243 AC: 26

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	0.091
BayesDel_addAF	Benign	-0.49	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.32
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.57	T
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.036	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		0.56
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-0.92	N
REVEL	Benign	0.065
Sift	Benign	0.070	T
Sift4G	Benign	0.28	T
Polyphen		0.66	P
Vest4		0.23
MVP		0.26
MPC		1.5
ClinPred		0.052	T
GERP RS		2.4
Varity_R		0.059
gMVP		0.15
Mutation Taster		=94/6	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: rs368040702; hg19: chr7-99769192;