rs2230606

Variant names:

• chr1-198706934-A-C
• rs2230606
• NM_002838.5:c.886A>C

Your query was ambiguous. Multiple possible variants found:

• chr1-198706934-A-C
• chr1-198706934-A-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

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. 13/19 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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -4.26
• Publications: 15 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 -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 VariationId is 138848.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 33 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRC	NM_002838.5	c.886A>C	p.Ile296Leu	missense_variant	Exon 9 of 33	ENST00000442510.8	NP_002829.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPRC	ENST00000442510.8	c.886A>C	p.Ile296Leu	missense_variant	Exon 9 of 33	1	NM_002838.5	ENSP00000411355.3

Frequencies

GnomAD3 genomes AF: 0.0165 AC: 2509 AN: 152200 Hom.: 33 Cov.: 32

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

GnomAD2 exomes AF: 0.0175 AC: 4389 AN: 251218 AF XY: 0.0177

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 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.: 30 AF XY: 0.0175 AC XY: 12656 AN XY: 722586

African (AFR) AF: 0.00873 AC: 290 AN: 33216

American (AMR) AF: 0.0108 AC: 484 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.0513 AC: 1336 AN: 26068

East Asian (EAS) AF: 0.0000505 AC: 2 AN: 39590

South Asian (SAS) AF: 0.0125 AC: 1070 AN: 85918

European-Finnish (FIN) AF: 0.0474 AC: 2531 AN: 53400

Middle Eastern (MID) AF: 0.0168 AC: 96 AN: 5702

European-Non Finnish (NFE) AF: 0.0168 AC: 18574 AN: 1102654

Other (OTH) AF: 0.0188 AC: 1129 AN: 60062

GnomAD4 genome AF: 0.0165 AC: 2518 AN: 152318 Hom.: 33 Cov.: 32 AF XY: 0.0175 AC XY: 1304 AN XY: 74472

African (AFR) AF: 0.00835 AC: 347 AN: 41564

American (AMR) AF: 0.0144 AC: 220 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0527 AC: 183 AN: 3472

East Asian (EAS) AF: 0.000577 AC: 3 AN: 5196

South Asian (SAS) AF: 0.0116 AC: 56 AN: 4826

European-Finnish (FIN) AF: 0.0489 AC: 519 AN: 10614

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0168 AC: 1146 AN: 68026

Other (OTH) AF: 0.0166 AC: 35 AN: 2112

Alfa AF: 0.0165 Hom.: 71

Bravo AF: 0.0134

TwinsUK AF: 0.0194 AC: 72

ALSPAC AF: 0.0158 AC: 61

ESP6500AA AF: 0.00772 AC: 34

ESP6500EA AF: 0.0203 AC: 175

ExAC AF: 0.0159 AC: 1929

Asia WGS AF: 0.00780 AC: 28 AN: 3476

EpiCase AF: 0.0186

EpiControl AF: 0.0165

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Aug 02, 2013

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Immunodeficiency 104 Benign:1

Feb 01, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.64	T
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	N
LIST_S2	Benign	0.073	T;T;T;T;T
MetaRNN	Benign	0.0024	T;T;T;T;T
MetaSVM	Benign	-0.98	T
PhyloP100		-4.3
PrimateAI	Benign	0.26	T
REVEL	Benign	0.043
Sift4G	Benign	0.40	T;T;T;T;T
Vest4		0.13, 0.059
MPC		0.17
ClinPred		0.0041	T
GERP RS		-9.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.16
gMVP		0.26
Mutation Taster		=95/5	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: rs2230606; hg19: chr1-198676063;