NM_002838.5:c.1865-304G>A

Variant names:

• chr1-198731313-G-A
• rs10919563
• NM_002838.5:c.1865-304G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002838.5(PTPRC):​c.1865-304G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 151,850 control chromosomes in the GnomAD database, including 4,464 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.21 (4464 hom., cov: 32)
• Consequence: PTPRC NM_002838.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.239
• Publications: 60 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 1-198731313-G-A is Benign according to our data. Variant chr1-198731313-G-A is described in ClinVar as Benign. ClinVar VariationId is 1261380.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.379 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.1865-304G>A		intron	N/A	NP_002829.3
	PTPRC	NM_080921.4		c.1382-304G>A		intron	N/A	NP_563578.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRC	ENST00000442510.8	TSL:1 MANE Select	c.1865-304G>A		intron	N/A	ENSP00000411355.3
	PTPRC	ENST00000348564.12	TSL:1	c.1382-304G>A		intron	N/A	ENSP00000306782.7
	PTPRC	ENST00000530727.5	TSL:1	c.1523-304G>A		intron	N/A	ENSP00000433536.2

Frequencies

GnomAD3 genomes AF: 0.211 AC: 31955 AN: 151734 Hom.: 4448 Cov.: 32

Gnomad AFR AF: 0.384

Gnomad AMI AF: 0.0835

Gnomad AMR AF: 0.236

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.256

Gnomad SAS AF: 0.210

Gnomad FIN AF: 0.0677

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.191

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

GnomAD4 genome AF: 0.211 AC: 32012 AN: 151850 Hom.: 4464 Cov.: 32 AF XY: 0.207 AC XY: 15383 AN XY: 74236

African (AFR) AF: 0.384 AC: 15879 AN: 41382

American (AMR) AF: 0.236 AC: 3594 AN: 15204

Ashkenazi Jewish (ASJ) AF: 0.105 AC: 364 AN: 3466

East Asian (EAS) AF: 0.256 AC: 1321 AN: 5158

South Asian (SAS) AF: 0.209 AC: 1007 AN: 4818

European-Finnish (FIN) AF: 0.0677 AC: 716 AN: 10574

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.127 AC: 8607 AN: 67928

Other (OTH) AF: 0.191 AC: 404 AN: 2116

Alfa AF: 0.171 Hom.: 4945

Bravo AF: 0.232

Asia WGS AF: 0.236 AC: 819 AN: 3470

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jul 09, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.5
DANN	Benign	0.54
PhyloP100		0.24
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs10919563; hg19: chr1-198700442;