rs2904269

Variant names:

• chr20-50539794-C-A
• rs2904269
• NM_002827.4:c.64-21569C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002827.4(PTPN1):​c.64-21569C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.519 in 151,400 control chromosomes in the GnomAD database, including 21,003 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.52 (21003 hom., cov: 29)
• Consequence: PTPN1 NM_002827.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.972
• Publications: 4 publications found

Genes affected

PTPN1 (HGNC:9642): (protein tyrosine phosphatase non-receptor type 1) The protein encoded by this gene is the founding member of the protein tyrosine phosphatase (PTP) family, which was isolated and identified based on its enzymatic activity and amino acid sequence. PTPs catalyze the hydrolysis of the phosphate monoesters specifically on tyrosine residues. Members of the PTP family share a highly conserved catalytic motif, which is essential for the catalytic activity. 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 has been shown to act as a negative regulator of insulin signaling by dephosphorylating the phosphotryosine residues of insulin receptor kinase. This PTP was also reported to dephosphorylate epidermal growth factor receptor kinase, as well as JAK2 and TYK2 kinases, which implicated the role of this PTP in cell growth control, and cell response to interferon stimulation. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2013]

PTPN1 Gene-Disease associations (from GenCC):

• autoinflammatory syndrome

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.657 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002827.4. 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
	PTPN1	NM_002827.4	MANE Select	c.64-21569C>A		intron	N/A	NP_002818.1	A8K3M3
	PTPN1	NM_001278618.2		c.-65-25175C>A		intron	N/A	NP_001265547.1	B4DSN5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPN1	ENST00000371621.5	TSL:1 MANE Select	c.64-21569C>A		intron	N/A	ENSP00000360683.3	P18031
	PTPN1	ENST00000859846.1		c.64-21569C>A		intron	N/A	ENSP00000529905.1
	PTPN1	ENST00000859845.1		c.64-21569C>A		intron	N/A	ENSP00000529904.1

Frequencies

GnomAD3 genomes AF: 0.519 AC: 78506 AN: 151282 Hom.: 20964 Cov.: 29

Gnomad AFR AF: 0.663

Gnomad AMI AF: 0.424

Gnomad AMR AF: 0.492

Gnomad ASJ AF: 0.465

Gnomad EAS AF: 0.318

Gnomad SAS AF: 0.377

Gnomad FIN AF: 0.463

Gnomad MID AF: 0.365

Gnomad NFE AF: 0.477

Gnomad OTH AF: 0.487

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.519 AC: 78604 AN: 151400 Hom.: 21003 Cov.: 29 AF XY: 0.517 AC XY: 38208 AN XY: 73940

African (AFR) AF: 0.664 AC: 27415 AN: 41308

American (AMR) AF: 0.492 AC: 7500 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.465 AC: 1607 AN: 3454

East Asian (EAS) AF: 0.318 AC: 1640 AN: 5156

South Asian (SAS) AF: 0.377 AC: 1805 AN: 4790

European-Finnish (FIN) AF: 0.463 AC: 4786 AN: 10338

Middle Eastern (MID) AF: 0.355 AC: 103 AN: 290

European-Non Finnish (NFE) AF: 0.477 AC: 32345 AN: 67824

Other (OTH) AF: 0.484 AC: 1019 AN: 2104

Alfa AF: 0.520 Hom.: 2727

Bravo AF: 0.528

Asia WGS AF: 0.374 AC: 1300 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.13
DANN	Benign	0.63
PhyloP100		-0.97
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2904269; hg19: chr20-49156331;