chr12-70534620-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PP3_ModerateBS2

The NM_001109754.4(PTPRB):​c.6236G>A​(p.Arg2079His) variant causes a missense change. The variant allele was found at a frequency of 0.00000616 in 1,460,358 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R2079C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

PTPRB
NM_001109754.4 missense

Scores

6
9
3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.05
Variant links:
Genes affected
PTPRB (HGNC:9665): (protein tyrosine phosphatase receptor type B) 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, mitotic cycle, and oncogenic transformation. This PTP contains an extracellular domain, a single transmembrane segment and one intracytoplasmic catalytic domain, thus belongs to receptor type PTP. The extracellular region of this PTP is composed of multiple fibronectin type_III repeats, which was shown to interact with neuronal receptor and cell adhesion molecules, such as contactin and tenascin C. This protein was also found to interact with sodium channels, and thus may regulate sodium channels by altering tyrosine phosphorylation status. The functions of the interaction partners of this protein implicate the roles of this PTP in cell adhesion, neurite growth, and neuronal differentiation. Alternate transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2011]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PP3
MetaRNN computational evidence supports a deleterious effect, 0.868
BS2
High AC in GnomAdExome4 at 9 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PTPRBNM_001109754.4 linkc.6236G>A p.Arg2079His missense_variant Exon 31 of 34 ENST00000334414.11 NP_001103224.1 P23467-3Q86VA4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PTPRBENST00000334414.11 linkc.6236G>A p.Arg2079His missense_variant Exon 31 of 34 1 NM_001109754.4 ENSP00000334928.6 P23467-3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000812
AC:
2
AN:
246428
Hom.:
0
AF XY:
0.00000748
AC XY:
1
AN XY:
133634
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000179
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000616
AC:
9
AN:
1460358
Hom.:
0
Cov.:
32
AF XY:
0.00000964
AC XY:
7
AN XY:
726296
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000720
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.00000827
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 07, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.6236G>A (p.R2079H) alteration is located in exon 31 (coding exon 31) of the PTPRB gene. This alteration results from a G to A substitution at nucleotide position 6236, causing the arginine (R) at amino acid position 2079 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.33
D
BayesDel_noAF
Pathogenic
0.25
CADD
Pathogenic
32
DANN
Pathogenic
1.0
DEOGEN2
Uncertain
0.63
.;D;.;.;D
Eigen
Uncertain
0.68
Eigen_PC
Pathogenic
0.70
FATHMM_MKL
Uncertain
0.90
D
LIST_S2
Uncertain
0.96
D;D;D;D;D
M_CAP
Benign
0.064
D
MetaRNN
Pathogenic
0.87
D;D;D;D;D
MetaSVM
Uncertain
0.36
D
MutationAssessor
Benign
1.2
.;.;.;.;L
PrimateAI
Uncertain
0.69
T
PROVEAN
Uncertain
-3.6
D;D;D;D;D
REVEL
Pathogenic
0.72
Sift
Uncertain
0.0040
D;D;D;D;D
Sift4G
Uncertain
0.016
D;D;D;D;D
Polyphen
1.0
D;D;.;D;D
Vest4
0.76
MutPred
0.67
.;Gain of catalytic residue at Y1995 (P = 0.0095);.;.;.;
MVP
0.92
MPC
1.4
ClinPred
0.99
D
GERP RS
5.7
Varity_R
0.80
gMVP
0.67

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.

Other links and lift over

dbSNP: rs748022415; hg19: chr12-70928400; API