rs2302224

Positions:

• chr19-5210611-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002850.4(PTPRS):​c.5362-17C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 1,613,776 control chromosomes in the GnomAD database, including 55,393 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.28 (6200 hom., cov: 33)
  • Exomes 𝑓: 0.26 (49193 hom.)
• Consequence: PTPRS NM_002850.4 splice_polypyrimidine_tract, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.21

Genes affected

PTPRS (HGNC:9681): (protein tyrosine phosphatase receptor type S) 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 region, a single transmembrane segment and two tandem intracytoplasmic catalytic domains, and thus represents a receptor-type PTP. The extracellular region of this protein is composed of multiple Ig-like and fibronectin type III-like domains. Studies of the similar gene in mice suggested that this PTP may be involved in cell-cell interaction, primary axonogenesis, and axon guidance during embryogenesis. This PTP has been also implicated in the molecular control of adult nerve repair. Four alternatively spliced transcript variants, which encode distinct proteins, have been reported. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: This place is a probable branch point but likely benign (scored 1 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.336 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTPRS	NM_002850.4	c.5362-17C>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000262963.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTPRS	ENST00000262963.11	c.5362-17C>T		splice_polypyrimidine_tract_variant, intron_variant		5	NM_002850.4	A1

Frequencies

GnomAD3 genomes AF: 0.282 AC: 42815 AN: 152020 Hom.: 6193 Cov.: 33

Gnomad AFR AF: 0.341

Gnomad AMI AF: 0.145

Gnomad AMR AF: 0.335

Gnomad ASJ AF: 0.281

Gnomad EAS AF: 0.0829

Gnomad SAS AF: 0.275

Gnomad FIN AF: 0.260

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.254

Gnomad OTH AF: 0.298

GnomAD3 exomes AF: 0.265 AC: 66490 AN: 250588 Hom.: 9493 AF XY: 0.261 AC XY: 35421 AN XY: 135504

Gnomad AFR exome AF: 0.349

Gnomad AMR exome AF: 0.354

Gnomad ASJ exome AF: 0.279

Gnomad EAS exome AF: 0.0758

Gnomad SAS exome AF: 0.266

Gnomad FIN exome AF: 0.257

Gnomad NFE exome AF: 0.257

Gnomad OTH exome AF: 0.268

GnomAD4 exome AF: 0.255 AC: 373392 AN: 1461638 Hom.: 49193 Cov.: 35 AF XY: 0.254 AC XY: 185023 AN XY: 727098

Gnomad4 AFR exome AF: 0.352

Gnomad4 AMR exome AF: 0.355

Gnomad4 ASJ exome AF: 0.281

Gnomad4 EAS exome AF: 0.0728

Gnomad4 SAS exome AF: 0.264

Gnomad4 FIN exome AF: 0.260

Gnomad4 NFE exome AF: 0.253

Gnomad4 OTH exome AF: 0.260

GnomAD4 genome AF: 0.282 AC: 42847 AN: 152138 Hom.: 6200 Cov.: 33 AF XY: 0.281 AC XY: 20891 AN XY: 74372

Gnomad4 AFR AF: 0.341

Gnomad4 AMR AF: 0.335

Gnomad4 ASJ AF: 0.281

Gnomad4 EAS AF: 0.0827

Gnomad4 SAS AF: 0.276

Gnomad4 FIN AF: 0.260

Gnomad4 NFE AF: 0.254

Gnomad4 OTH AF: 0.295

Alfa AF: 0.259 Hom.: 7956

Bravo AF: 0.288

Asia WGS AF: 0.209 AC: 727 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.012
DANN	Benign	0.66
BranchPoint Hunter		1.0

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

Other links and lift over

dbSNP: rs2302224; hg19: chr19-5210622;