rs2270993

Variant names:

• chr11-48123614-G-A
• rs2270993
• NM_002843.4:c.618G>A

Your query was ambiguous. Multiple possible variants found:

• chr11-48123614-G-A
• chr11-48123614-G-C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_002843.4(PTPRJ):​c.618G>A​(p.Glu206Glu) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 1,611,380 control chromosomes in the GnomAD database, including 16,856 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.16 (2322 hom., cov: 32)
  • Exomes 𝑓: 0.14 (14534 hom.)
• Consequence: PTPRJ NM_002843.4 splice_region, synonymous
• Scores: Splicing: ADA: 0.00005608
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.235
• Publications: 16 publications found

Genes affected

PTPRJ (HGNC:9673): (protein tyrosine phosphatase receptor type J) 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 containing five fibronectin type III repeats, a single transmembrane region, and a single intracytoplasmic catalytic domain, and thus represents a receptor-type PTP. This protein is present in all hematopoietic lineages, and was shown to negatively regulate T cell receptor signaling possibly through interfering with the phosphorylation of Phospholipase C Gamma 1 and Linker for Activation of T Cells. This protein can also dephosphorylate the PDGF beta receptor, and may be involved in UV-induced signal transduction. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

PTPRJ Gene-Disease associations (from GenCC):

• hereditary nonpolyposis colon cancer

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen
• thrombocytopenia 10

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics
• colorectal cancer

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP7: Synonymous conserved (PhyloP=-0.235 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.237 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRJ	NM_002843.4	c.618G>A	p.Glu206Glu	splice_region_variant, synonymous_variant	Exon 5 of 25	ENST00000418331.7	NP_002834.3
PTPRJ	NM_001098503.2	c.618G>A	p.Glu206Glu	splice_region_variant, synonymous_variant	Exon 5 of 9		NP_001091973.1
PTPRJ	XM_017018085.2	c.570G>A	p.Glu190Glu	splice_region_variant, synonymous_variant	Exon 5 of 25		XP_016873574.1
PTPRJ	XM_047427374.1	c.960G>A	p.Glu320Glu	splice_region_variant, synonymous_variant	Exon 5 of 17		XP_047283330.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPRJ	ENST00000418331.7	c.618G>A	p.Glu206Glu	splice_region_variant, synonymous_variant	Exon 5 of 25	1	NM_002843.4	ENSP00000400010.2
PTPRJ	ENST00000440289.6	c.618G>A	p.Glu206Glu	splice_region_variant, synonymous_variant	Exon 5 of 9	1		ENSP00000409733.2
PTPRJ	ENST00000698881.1	c.960G>A	p.Glu320Glu	splice_region_variant, synonymous_variant	Exon 5 of 25			ENSP00000514003.1
PTPRJ	ENST00000527952.1	c.354G>A	p.Glu118Glu	splice_region_variant, synonymous_variant	Exon 4 of 4	5		ENSP00000435618.1

Frequencies

GnomAD3 genomes AF: 0.164 AC: 24849 AN: 151960 Hom.: 2320 Cov.: 32

Gnomad AFR AF: 0.242

Gnomad AMI AF: 0.0768

Gnomad AMR AF: 0.119

Gnomad ASJ AF: 0.114

Gnomad EAS AF: 0.161

Gnomad SAS AF: 0.129

Gnomad FIN AF: 0.174

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.132

Gnomad OTH AF: 0.128

GnomAD2 exomes AF: 0.140 AC: 35053 AN: 250092 AF XY: 0.138

Gnomad AFR exome AF: 0.236

Gnomad AMR exome AF: 0.123

Gnomad ASJ exome AF: 0.112

Gnomad EAS exome AF: 0.165

Gnomad FIN exome AF: 0.164

Gnomad NFE exome AF: 0.129

Gnomad OTH exome AF: 0.108

GnomAD4 exome AF: 0.137 AC: 200356 AN: 1459302 Hom.: 14534 Cov.: 31 AF XY: 0.136 AC XY: 99023 AN XY: 725820

African (AFR) AF: 0.240 AC: 7996 AN: 33330

American (AMR) AF: 0.124 AC: 5507 AN: 44400

Ashkenazi Jewish (ASJ) AF: 0.110 AC: 2859 AN: 26050

East Asian (EAS) AF: 0.164 AC: 6506 AN: 39666

South Asian (SAS) AF: 0.139 AC: 11936 AN: 86070

European-Finnish (FIN) AF: 0.160 AC: 8556 AN: 53394

Middle Eastern (MID) AF: 0.106 AC: 576 AN: 5456

European-Non Finnish (NFE) AF: 0.134 AC: 148588 AN: 1110704

Other (OTH) AF: 0.130 AC: 7832 AN: 60232

GnomAD4 genome AF: 0.163 AC: 24859 AN: 152078 Hom.: 2322 Cov.: 32 AF XY: 0.164 AC XY: 12226 AN XY: 74344

African (AFR) AF: 0.241 AC: 10005 AN: 41460

American (AMR) AF: 0.119 AC: 1821 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.114 AC: 394 AN: 3468

East Asian (EAS) AF: 0.161 AC: 831 AN: 5156

South Asian (SAS) AF: 0.130 AC: 624 AN: 4812

European-Finnish (FIN) AF: 0.174 AC: 1839 AN: 10570

Middle Eastern (MID) AF: 0.134 AC: 39 AN: 292

European-Non Finnish (NFE) AF: 0.132 AC: 8971 AN: 68002

Other (OTH) AF: 0.126 AC: 265 AN: 2108

Alfa AF: 0.139 Hom.: 1536

Bravo AF: 0.162

Asia WGS AF: 0.130 AC: 451 AN: 3478

EpiCase AF: 0.118

EpiControl AF: 0.113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	1.1
DANN	Benign	0.39
PhyloP100		-0.23
Mutation Taster		=74/26	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000056
dbscSNV1_RF	Benign	0.020
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: rs2270993; hg19: chr11-48145166; COSMIC: COSV69250633; COSMIC: COSV69250633;