12-70524533-C-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001109754.4(PTPRB):c.6563G>A(p.Arg2188Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000347 in 1,613,174 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R2188W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000034 ( 0 hom. )

Consequence

PTPRB
NM_001109754.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.85

Publications

0 publications found

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]

PTPRB links:

PTPRB-AS1 (HGNC:58150):

PTPRB-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High AC in GnomAd4 at 7 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001109754.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PTPRB	NM_001109754.4	MANE Select	c.6563G>A	p.Arg2188Gln	missense	Exon 33 of 34	NP_001103224.1	P23467-3
PTPRB	NM_001330204.2		c.6299G>A	p.Arg2100Gln	missense	Exon 32 of 33	NP_001317133.1	F8VU56
PTPRB	NM_002837.6		c.5909G>A	p.Arg1970Gln	missense	Exon 31 of 32	NP_002828.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PTPRB	ENST00000334414.11	TSL:1 MANE Select	c.6563G>A	p.Arg2188Gln	missense	Exon 33 of 34	ENSP00000334928.6	P23467-3
PTPRB	ENST00000261266.9	TSL:1	c.5909G>A	p.Arg1970Gln	missense	Exon 31 of 32	ENSP00000261266.5	P23467-1
PTPRB	ENST00000538708.5	TSL:1	c.5639G>A	p.Arg1880Gln	missense	Exon 30 of 31	ENSP00000438927.1	P23467-4

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152046

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000281

AC:

AN:

248824

AF XY:

0.0000222

show subpopulations

Gnomad AFR exome

AF:

0.000129

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000887

Gnomad OTH exome

AF:

0.000332

GnomAD4 exome

AF:

0.0000335

AC:

AN:

1461012

Hom.:

Cov.:

AF XY:

0.0000234

AC XY:

AN XY:

726826

show subpopulations

African (AFR)

AF:

0.000478

AC:

AN:

33462

American (AMR)

AF:

0.0000224

AC:

AN:

44688

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39684

South Asian (SAS)

AF:

0.0000348

AC:

AN:

86246

European-Finnish (FIN)

AF:

0.0000187

AC:

AN:

53390

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.0000198

AC:

AN:

1111298

Other (OTH)

AF:

0.0000828

AC:

AN:

60350

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152162

Hom.:

Cov.:

AF XY:

0.0000672

AC XY:

AN XY:

74384

show subpopulations

African (AFR)

AF:

0.000120

AC:

AN:

41522

American (AMR)

AF:

0.0000655

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4806

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10602

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67992

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000596

Hom.:

Bravo

AF:

0.0000756

ESP6500AA

AF:

0.000264

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000331

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.30

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.31

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.072

Eigen

Uncertain

0.62

Eigen_PC

Uncertain

0.66

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Pathogenic

0.99

M_CAP

Benign

0.027

MetaRNN

Uncertain

0.45

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.97

PhyloP100

5.8

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-1.4

REVEL

Benign

0.20

Sift

Uncertain

0.0090

Sift4G

Uncertain

0.015

Polyphen

1.0

Vest4

0.66

MVP

0.51

MPC

1.3

ClinPred

0.40

GERP RS

5.7

Varity_R

0.90

gMVP

0.62

Mutation Taster

=63/37

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over