rs2302224

Variant names:

• chr19-5210611-G-A
• rs2302224
• NM_002850.4:c.5362-17C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002850.4(PTPRS):​c.5362-17C>T variant causes a 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 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.21
• Publications: 9 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 1 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. 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 rank	MANE	Protein	UniProt
PTPRS	NM_002850.4	c.5362-17C>T		intron_variant	Intron 34 of 37	ENST00000262963.11	NP_002841.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPRS	ENST00000262963.11	c.5362-17C>T		intron_variant	Intron 34 of 37	5	NM_002850.4	ENSP00000262963.8

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

GnomAD2 exomes AF: 0.265 AC: 66490 AN: 250588 AF XY: 0.261

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 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

African (AFR) AF: 0.352 AC: 11779 AN: 33480

American (AMR) AF: 0.355 AC: 15858 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.281 AC: 7351 AN: 26132

East Asian (EAS) AF: 0.0728 AC: 2891 AN: 39696

South Asian (SAS) AF: 0.264 AC: 22740 AN: 86250

European-Finnish (FIN) AF: 0.260 AC: 13883 AN: 53306

Middle Eastern (MID) AF: 0.282 AC: 1628 AN: 5766

European-Non Finnish (NFE) AF: 0.253 AC: 281544 AN: 1111924

Other (OTH) AF: 0.260 AC: 15718 AN: 60386

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

African (AFR) AF: 0.341 AC: 14138 AN: 41476

American (AMR) AF: 0.335 AC: 5113 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.281 AC: 975 AN: 3470

East Asian (EAS) AF: 0.0827 AC: 428 AN: 5178

South Asian (SAS) AF: 0.276 AC: 1333 AN: 4828

European-Finnish (FIN) AF: 0.260 AC: 2758 AN: 10598

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.254 AC: 17254 AN: 67992

Other (OTH) AF: 0.295 AC: 622 AN: 2110

Alfa AF: 0.262 Hom.: 13858

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
PhyloP100		-2.2
BranchPoint Hunter		1.0
Mutation Taster		=100/0	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: rs2302224; hg19: chr19-5210622; COSMIC: COSV107304327; COSMIC: COSV107304327;