NM_002843.4:c.77_85dupTGCTGCTGC

Variant names:

• chr11-47980977-C-CGCTGCTGCT
• rs747484779
• NM_002843.4:c.77_85dupTGCTGCTGC

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP3

The NM_002843.4(PTPRJ):​c.77_85dupTGCTGCTGC​(p.Leu26_Leu28dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000134 in 1,191,832 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000068 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: PTPRJ NM_002843.4 disruptive_inframe_insertion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.197
• Publications: 1 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, ClinGen
• colorectal cancer

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

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_002843.4

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002843.4. 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
	PTPRJ	NM_002843.4	MANE Select	c.77_85dupTGCTGCTGC	p.Leu26_Leu28dup	disruptive_inframe_insertion	Exon 1 of 25	NP_002834.3
	PTPRJ	NM_001098503.2		c.77_85dupTGCTGCTGC	p.Leu26_Leu28dup	disruptive_inframe_insertion	Exon 1 of 9	NP_001091973.1	Q12913-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRJ	ENST00000418331.7	TSL:1 MANE Select	c.77_85dupTGCTGCTGC	p.Leu26_Leu28dup	disruptive_inframe_insertion	Exon 1 of 25	ENSP00000400010.2	Q12913-1
	PTPRJ	ENST00000440289.6	TSL:1	c.77_85dupTGCTGCTGC	p.Leu26_Leu28dup	disruptive_inframe_insertion	Exon 1 of 9	ENSP00000409733.2	Q12913-2
	PTPRJ	ENST00000698881.1		c.419_427dupTGCTGCTGC	p.Leu140_Leu142dup	disruptive_inframe_insertion	Exon 1 of 25	ENSP00000514003.1	A0A8V8TP51

Frequencies

GnomAD3 genomes AF: 0.00000681 AC: 1 AN: 146754 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000248

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000144 AC: 15 AN: 1045078 Hom.: 0 Cov.: 31 AF XY: 0.0000203 AC XY: 10 AN XY: 492898

African (AFR) AF: 0.0000461 AC: 1 AN: 21680

American (AMR) AF: 0.00 AC: 0 AN: 7142

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12892

East Asian (EAS) AF: 0.00 AC: 0 AN: 24360

South Asian (SAS) AF: 0.0000523 AC: 1 AN: 19136

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 18714

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2730

European-Non Finnish (NFE) AF: 0.0000145 AC: 13 AN: 897270

Other (OTH) AF: 0.00 AC: 0 AN: 41154

GnomAD4 genome AF: 0.00000681 AC: 1 AN: 146754 Hom.: 0 Cov.: 32 AF XY: 0.0000140 AC XY: 1 AN XY: 71394

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000248 AC: 1 AN: 40398

American (AMR) AF: 0.00 AC: 0 AN: 14886

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3390

East Asian (EAS) AF: 0.00 AC: 0 AN: 4744

South Asian (SAS) AF: 0.00 AC: 0 AN: 4540

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9284

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 298

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 66346

Other (OTH) AF: 0.00 AC: 0 AN: 2006

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.20
Mutation Taster		=77/23	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs747484779; hg19: chr11-48002529;