rs2230606

Positions:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_002838.5(PTPRC):c.886A>C(p.Ile296Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0175 in 1,603,636 control chromosomes in the GnomAD database, including 359 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.017 ( 33 hom., cov: 32)

Exomes 𝑓: 0.018 ( 326 hom. )

Consequence

PTPRC
NM_002838.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -4.26

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002391249).

BP6

Variant 1-198706934-A-C is Benign according to our data. Variant chr1-198706934-A-C is described in ClinVar as [Benign]. Clinvar id is 138848.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-198706934-A-C is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0165 (2518/152318) while in subpopulation NFE AF= 0.0168 (1146/68026). AF 95% confidence interval is 0.016. There are 33 homozygotes in gnomad4. There are 1304 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 33 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTPRC	NM_002838.5 linkuse as main transcript	c.886A>C	p.Ile296Leu	missense_variant	9/33	ENST00000442510.8	NP_002829.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTPRC	ENST00000442510.8 linkuse as main transcript	c.886A>C	p.Ile296Leu	missense_variant	9/33	1	NM_002838.5	ENSP00000411355	A2	P08575-3

Frequencies

GnomAD3 genomes

AF:

0.0165

AC:

2509

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00818

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.0144

Gnomad ASJ

AF:

0.0527

Gnomad EAS

AF:

0.000576

Gnomad SAS

AF:

0.0114

Gnomad FIN

AF:

0.0489

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0168

Gnomad OTH

AF:

0.0167

GnomAD3 exomes

AF:

0.0175

AC:

4389

AN:

251218

Hom.:

AF XY:

0.0177

AC XY:

2407

AN XY:

135790

show subpopulations

Gnomad AFR exome

AF:

0.00813

Gnomad AMR exome

AF:

0.0104

Gnomad ASJ exome

AF:

0.0507

Gnomad EAS exome

AF:

0.000217

Gnomad SAS exome

AF:

0.0122

Gnomad FIN exome

AF:

0.0487

Gnomad NFE exome

AF:

0.0163

Gnomad OTH exome

AF:

0.0180

GnomAD4 exome

AF:

0.0176

AC:

25512

AN:

1451318

Hom.:

326

Cov.:

AF XY:

0.0175

AC XY:

12656

AN XY:

722586

show subpopulations

Gnomad4 AFR exome

AF:

0.00873

Gnomad4 AMR exome

AF:

0.0108

Gnomad4 ASJ exome

AF:

0.0513

Gnomad4 EAS exome

AF:

0.0000505

Gnomad4 SAS exome

AF:

0.0125

Gnomad4 FIN exome

AF:

0.0474

Gnomad4 NFE exome

AF:

0.0168

Gnomad4 OTH exome

AF:

0.0188

GnomAD4 genome

AF:

0.0165

AC:

2518

AN:

152318

Hom.:

Cov.:

AF XY:

0.0175

AC XY:

1304

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.00835

Gnomad4 AMR

AF:

0.0144

Gnomad4 ASJ

AF:

0.0527

Gnomad4 EAS

AF:

0.000577

Gnomad4 SAS

AF:

0.0116

Gnomad4 FIN

AF:

0.0489

Gnomad4 NFE

AF:

0.0168

Gnomad4 OTH

AF:

0.0166

Alfa

AF:

0.0166

Hom.:

Bravo

AF:

0.0134

TwinsUK

AF:

0.0194

AC:

ALSPAC

AF:

0.0158

AC:

ESP6500AA

AF:

0.00772

AC:

ESP6500EA

AF:

0.0203

AC:

175

ExAC

AF:

0.0159

AC:

1929

Asia WGS

AF:

0.00780

AC:

AN:

3476

EpiCase

AF:

0.0186

EpiControl

AF:

0.0165

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 02, 2013

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Immunodeficiency 104

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.67

CADD

Benign

0.0010

DANN

Benign

0.65

DEOGEN2

Benign

0.0071

.;.;.;T;T

Eigen

Benign

-2.5

Eigen_PC

Benign

-2.6

FATHMM_MKL

Benign

0.0049

LIST_S2

Benign

0.073

T;T;T;T;T

MetaRNN

Benign

0.0024

T;T;T;T;T

MetaSVM

Benign

-0.98

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.26

REVEL

Benign

0.043

Sift4G

Benign

0.40

T;T;T;T;T

Vest4

0.13, 0.059

MPC

0.17

ClinPred

0.0041

GERP RS

-9.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.16

gMVP

0.26

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over