chr12-70534512-G-A

Position:

• chr12-70534512-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001109754.4(PTPRB):​c.6344C>T​(p.Ala2115Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,460,704 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: PTPRB NM_001109754.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.63

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]

ENSG00000258168 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29480785).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTPRB	NM_001109754.4	c.6344C>T	p.Ala2115Val	missense_variant	31/34	ENST00000334414.11	NP_001103224.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTPRB	ENST00000334414.11	c.6344C>T	p.Ala2115Val	missense_variant	31/34	1	NM_001109754.4	ENSP00000334928.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460704 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 726564

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: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 16, 2022

The c.6344C>T (p.A2115V) alteration is located in exon 31 (coding exon 31) of the PTPRB gene. This alteration results from a C to T substitution at nucleotide position 6344, causing the alanine (A) at amino acid position 2115 to be replaced by a valine (V). 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	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.26	.;T;.;.;T
Eigen	Benign	0.052
Eigen_PC	Benign	0.10
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.84	T;D;T;T;T
M_CAP	Benign	0.0076	T
MetaRNN	Benign	0.29	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.070	.;.;.;.;N
MutationTaster	Benign	1.0	N;N;N;N;N;N
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-1.3	N;N;N;N;N
REVEL	Benign	0.12
Sift	Benign	0.034	D;D;D;D;T
Sift4G	Uncertain	0.042	D;D;D;T;D
Polyphen		0.92	P;P;.;P;P
Vest4		0.35
MutPred		0.43		.;Gain of catalytic residue at R2023 (P = 0);.;.;.;
MVP		0.23
MPC		0.52
ClinPred		0.43	T
GERP RS		5.7
Varity_R		0.21
gMVP		0.39

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-70928292;