PTPN22 p.Arg266Arg

Variant names:

• chr1-113852056-T-T
• NM_015967.8:c.

Your query was ambiguous. Multiple possible variants found:

• chr1-113852057--
• chr1-113852057-C-A
• chr1-113852057-C-G
• chr1-113852057-C-T
• chr1-113852059-G-T
• chr1-113852057-CCG-TCT

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_015967.8(PTPN22):​c. variant causes a exon region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PTPN22 NM_015967.8 exon_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.587
• Publications: 0 publications found

Genes affected

PTPN22 (HGNC:9652): (protein tyrosine phosphatase non-receptor type 22) This gene encodes of member of the non-receptor class 4 subfamily of the protein-tyrosine phosphatase family. The encoded protein is a lymphoid-specific intracellular phosphatase that associates with the molecular adapter protein CBL and may be involved in regulating CBL function in the T-cell receptor signaling pathway. Mutations in this gene may be associated with a range of autoimmune disorders including Type 1 Diabetes, rheumatoid arthritis, systemic lupus erythematosus and Graves' disease. Alternatively spliced transcript variants encoding distinct isoforms have been described. [provided by RefSeq, Mar 2009]

AP4B1-AS1 (HGNC:44114): (AP4B1 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015967.8. 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
	PTPN22	NM_015967.8	MANE Select	c.		exon_region	Exon 10 of 21	NP_057051.4
	PTPN22	NM_001308297.2		c.		exon_region	Exon 9 of 20	NP_001295226.2	F5H2S8
	PTPN22	NM_001193431.3		c.		exon_region	Exon 10 of 21	NP_001180360.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPN22	ENST00000359785.10	TSL:1 MANE Select	c.		exon_region	Exon 10 of 21	ENSP00000352833.5	A0A0B4J1S7
	PTPN22	ENST00000420377.6	TSL:1	c.		exon_region	Exon 10 of 20	ENSP00000388229.2	E9PMT0
	PTPN22	ENST00000538253.5	TSL:1	c.		exon_region	Exon 9 of 20	ENSP00000439372.2	F5H2S8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.59

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr1-114394678;