chr20-50513582-C-G

Variant names:

• chr20-50513582-C-G
• rs2206656
• NM_002827.4:c.63+2992C>G

Variant summary

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

The NM_002827.4(PTPN1):​c.63+2992C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.424 in 151,990 control chromosomes in the GnomAD database, including 13,949 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 0.42 (13949 hom., cov: 32)
• Consequence: PTPN1 NM_002827.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.58
• Publications: 9 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.525 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPN1	NM_002827.4	MANE Select	c.63+2992C>G		intron	N/A	NP_002818.1
	PTPN1	NM_001278618.2		c.-66+2992C>G		intron	N/A	NP_001265547.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPN1	ENST00000371621.5	TSL:1 MANE Select	c.63+2992C>G		intron	N/A	ENSP00000360683.3
	PTPN1	ENST00000541713.5	TSL:2	c.-66+2992C>G		intron	N/A	ENSP00000437732.1

Frequencies

GnomAD3 genomes AF: 0.424 AC: 64409 AN: 151872 Hom.: 13918 Cov.: 32

Gnomad AFR AF: 0.530

Gnomad AMI AF: 0.308

Gnomad AMR AF: 0.423

Gnomad ASJ AF: 0.376

Gnomad EAS AF: 0.299

Gnomad SAS AF: 0.337

Gnomad FIN AF: 0.365

Gnomad MID AF: 0.268

Gnomad NFE AF: 0.390

Gnomad OTH AF: 0.403

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

GnomAD4 genome AF: 0.424 AC: 64493 AN: 151990 Hom.: 13949 Cov.: 32 AF XY: 0.421 AC XY: 31273 AN XY: 74312

African (AFR) AF: 0.531 AC: 21998 AN: 41452

American (AMR) AF: 0.424 AC: 6476 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.376 AC: 1306 AN: 3472

East Asian (EAS) AF: 0.299 AC: 1548 AN: 5172

South Asian (SAS) AF: 0.337 AC: 1618 AN: 4806

European-Finnish (FIN) AF: 0.365 AC: 3854 AN: 10566

Middle Eastern (MID) AF: 0.257 AC: 75 AN: 292

European-Non Finnish (NFE) AF: 0.390 AC: 26495 AN: 67938

Other (OTH) AF: 0.401 AC: 843 AN: 2102

Alfa AF: 0.420 Hom.: 1722

Bravo AF: 0.434

Asia WGS AF: 0.339 AC: 1179 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	9.3
DANN	Benign	0.26
PhyloP100		1.6
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: rs2206656; hg19: chr20-49130119;