Genetic Variant NM_002843.4:c.80_85dupTGCTGC (chr11-47980977-C-CGCTGCT) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_002843.4(PTPRJ):c.80_85dupTGCTGC(p.Leu27_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 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

PTPRJ
NM_002843.4 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.197

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRJ	NM_002843.4 link	c.80_85dupTGCTGC	p.Leu27_Leu28dup	disruptive_inframe_insertion	Exon 1 of 25	ENST00000418331.7	NP_002834.3	Q12913-1Q9NPR5
PTPRJ	NM_001098503.2 link	c.80_85dupTGCTGC	p.Leu27_Leu28dup	disruptive_inframe_insertion	Exon 1 of 9		NP_001091973.1	Q12913-2
PTPRJ	XM_047427374.1 link	c.422_427dupTGCTGC	p.Leu141_Leu142dup	disruptive_inframe_insertion	Exon 1 of 17		XP_047283330.1
PTPRJ	XM_017018085.2 link	c.48+374_48+379dupTGCTGC		intron_variant	Intron 1 of 24		XP_016873574.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPRJ	ENST00000418331.7 link	c.80_85dupTGCTGC	p.Leu27_Leu28dup	disruptive_inframe_insertion	Exon 1 of 25	1	NM_002843.4	ENSP00000400010.2		Q12913-1

Frequencies

GnomAD3 genomes

AF:

0.0000204

AC:

AN:

146754

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000743

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:

0.0000124

AC:

AN:

1045078

Hom.:

Cov.:

AF XY:

0.0000122

AC XY:

AN XY:

492898

show subpopulations

Gnomad4 AFR exome

AF:

0.0000461

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000123

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000892

Gnomad4 OTH exome

AF:

0.0000243

GnomAD4 genome

AF:

0.0000204

AC:

AN:

146754

Hom.:

Cov.:

AF XY:

0.0000140

AC XY:

AN XY:

71394

show subpopulations

Gnomad4 AFR

AF:

0.0000743

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over