rs2359952

Variant names:

• chr1-198687278-A-G
• rs2359952
• NM_002838.5:c.74-5069A>G

Variant summary

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

The NM_002838.5(PTPRC):​c.74-5069A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.373 in 151,892 control chromosomes in the GnomAD database, including 11,009 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 0.37 (11009 hom., cov: 31)
• Consequence: PTPRC NM_002838.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.31
• Publications: 19 publications found

Genes affected

PTPRC (HGNC:9666): (protein tyrosine phosphatase receptor type C) 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, mitosis, and oncogenic transformation. This PTP contains an extracellular domain, a single transmembrane segment and two tandem intracytoplasmic catalytic domains, and thus is classified as a receptor type PTP. This PTP has been shown to be an essential regulator of T- and B-cell antigen receptor signaling. It functions through either direct interaction with components of the antigen receptor complexes, or by activating various Src family kinases required for the antigen receptor signaling. This PTP also suppresses JAK kinases, and thus functions as a regulator of cytokine receptor signaling. Alternatively spliced transcripts variants of this gene, which encode distinct isoforms, have been reported. [provided by RefSeq, Jun 2012]

PTPRC Gene-Disease associations (from GenCC):

• immunodeficiency 104

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae)
• T-B+ severe combined immunodeficiency due to CD45 deficiency

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.471 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002838.5. 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
	PTPRC	NM_002838.5	MANE Select	c.74-5069A>G		intron	N/A	NP_002829.3
	PTPRC	NM_080921.4		c.74-5069A>G		intron	N/A	NP_563578.2
	PTPRC	NM_001267798.2		c.74-5069A>G		intron	N/A	NP_001254727.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRC	ENST00000442510.8	TSL:1 MANE Select	c.74-5069A>G		intron	N/A	ENSP00000411355.3
	PTPRC	ENST00000348564.12	TSL:1	c.74-5069A>G		intron	N/A	ENSP00000306782.7
	PTPRC	ENST00000530727.5	TSL:1	c.74-5069A>G		intron	N/A	ENSP00000433536.2

Frequencies

GnomAD3 genomes AF: 0.372 AC: 56534 AN: 151774 Hom.: 10988 Cov.: 31

Gnomad AFR AF: 0.477

Gnomad AMI AF: 0.252

Gnomad AMR AF: 0.424

Gnomad ASJ AF: 0.388

Gnomad EAS AF: 0.370

Gnomad SAS AF: 0.410

Gnomad FIN AF: 0.278

Gnomad MID AF: 0.341

Gnomad NFE AF: 0.312

Gnomad OTH AF: 0.340

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

GnomAD4 genome AF: 0.373 AC: 56588 AN: 151892 Hom.: 11009 Cov.: 31 AF XY: 0.374 AC XY: 27759 AN XY: 74230

African (AFR) AF: 0.477 AC: 19733 AN: 41396

American (AMR) AF: 0.424 AC: 6474 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.388 AC: 1347 AN: 3470

East Asian (EAS) AF: 0.370 AC: 1911 AN: 5170

South Asian (SAS) AF: 0.410 AC: 1973 AN: 4818

European-Finnish (FIN) AF: 0.278 AC: 2933 AN: 10546

Middle Eastern (MID) AF: 0.325 AC: 95 AN: 292

European-Non Finnish (NFE) AF: 0.312 AC: 21176 AN: 67932

Other (OTH) AF: 0.340 AC: 717 AN: 2108

Alfa AF: 0.334 Hom.: 35105

Bravo AF: 0.390

Asia WGS AF: 0.434 AC: 1506 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.11
DANN	Benign	0.25
PhyloP100		-4.3
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: rs2359952; hg19: chr1-198656407;