rs2292245

Positions:

• chr3-62203515-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002841.4(PTPRG):​c.1720G>A​(p.Gly574Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 1,558,752 control chromosomes in the GnomAD database, including 24,644 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.17 (2325 hom., cov: 32)
  • Exomes 𝑓: 0.17 (22319 hom.)
• Consequence: PTPRG NM_002841.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.21

Genes affected

PTPRG (HGNC:9671): (protein tyrosine phosphatase receptor type G) The protein encoded by this gene is a member of the protein tyrosine phosphatase (PTP) family. PTPs are known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. This PTP possesses an extracellular region, a single transmembrane region, and two tandem intracytoplasmic catalytic domains, and thus represents a receptor-type PTP. The extracellular region of this PTP contains a carbonic anhydrase-like (CAH) domain, which is also found in the extracellular region of PTPRBETA/ZETA. This gene is located in a chromosomal region that is frequently deleted in renal cell carcinoma and lung carcinoma, thus is thought to be a candidate tumor suppressor gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.002423793).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.327 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTPRG	NM_002841.4	c.1720G>A	p.Gly574Ser	missense_variant	12/30	ENST00000474889.6	NP_002832.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTPRG	ENST00000474889.6	c.1720G>A	p.Gly574Ser	missense_variant	12/30	1	NM_002841.4	ENSP00000418112	A1
PTPRG	ENST00000295874.14	c.1720G>A	p.Gly574Ser	missense_variant	12/29	1		ENSP00000295874	P4

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25438 AN: 152032 Hom.: 2322 Cov.: 32

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.164

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.248

Gnomad EAS AF: 0.341

Gnomad SAS AF: 0.279

Gnomad FIN AF: 0.222

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.159

Gnomad OTH AF: 0.167

GnomAD3 exomes AF: 0.194 AC: 31747 AN: 164006 Hom.: 3505 AF XY: 0.201 AC XY: 17481 AN XY: 86910

Gnomad AFR exome AF: 0.136

Gnomad AMR exome AF: 0.108

Gnomad ASJ exome AF: 0.243

Gnomad EAS exome AF: 0.364

Gnomad SAS exome AF: 0.268

Gnomad FIN exome AF: 0.213

Gnomad NFE exome AF: 0.166

Gnomad OTH exome AF: 0.181

GnomAD4 exome AF: 0.173 AC: 243502 AN: 1406602 Hom.: 22319 Cov.: 33 AF XY: 0.176 AC XY: 122462 AN XY: 694688

Gnomad4 AFR exome AF: 0.137

Gnomad4 AMR exome AF: 0.108

Gnomad4 ASJ exome AF: 0.242

Gnomad4 EAS exome AF: 0.286

Gnomad4 SAS exome AF: 0.267

Gnomad4 FIN exome AF: 0.215

Gnomad4 NFE exome AF: 0.161

Gnomad4 OTH exome AF: 0.186

GnomAD4 genome AF: 0.167 AC: 25461 AN: 152150 Hom.: 2325 Cov.: 32 AF XY: 0.173 AC XY: 12883 AN XY: 74382

Gnomad4 AFR AF: 0.140

Gnomad4 AMR AF: 0.127

Gnomad4 ASJ AF: 0.248

Gnomad4 EAS AF: 0.341

Gnomad4 SAS AF: 0.278

Gnomad4 FIN AF: 0.222

Gnomad4 NFE AF: 0.159

Gnomad4 OTH AF: 0.169

Alfa AF: 0.170 Hom.: 5723

Bravo AF: 0.157

TwinsUK AF: 0.171 AC: 634

ALSPAC AF: 0.168 AC: 646

ESP6500AA AF: 0.135 AC: 586

ESP6500EA AF: 0.159 AC: 1350

ExAC AF: 0.140 AC: 15387

Asia WGS AF: 0.294 AC: 1024 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.77	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.030
DANN	Benign	0.89
DEOGEN2	Benign	0.068	.;T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0061	N
LIST_S2	Benign	0.35	T;T
MetaRNN	Benign	0.0024	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.20	N;N
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.47	T
PROVEAN	Benign	0.48	N;N
REVEL	Benign	0.042
Sift	Benign	0.72	T;T
Sift4G	Benign	0.65	T;T
Polyphen		0.098	B;B
Vest4		0.015
MPC		0.19
ClinPred		0.0047	T
GERP RS		-5.6
Varity_R		0.023
gMVP		0.097

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

Publications

LitVar

Other links and lift over

dbSNP: rs2292245; hg19: chr3-62189189; COSMIC: COSV55631922;