rs2238640

Variant names:

• chr19-5261495-G-A
• rs2238640
• NM_002850.4:c.578-673C>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.578-673C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.564 in 151,994 control chromosomes in the GnomAD database, including 26,637 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.

• Frequency: Genomes: 𝑓 0.56 (26637 hom., cov: 32)
• Consequence: PTPRS NM_002850.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.700
• Publications: 6 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: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.787 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002850.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRS	NM_002850.4	MANE Select	c.578-673C>T		intron	N/A	NP_002841.3
	PTPRS	NM_001394011.1		c.569-3368C>T		intron	N/A	NP_001380940.1
	PTPRS	NM_001394012.1		c.569-3368C>T		intron	N/A	NP_001380941.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRS	ENST00000262963.11	TSL:5 MANE Select	c.578-673C>T		intron	N/A	ENSP00000262963.8
	PTPRS	ENST00000587303.5	TSL:1	c.578-673C>T		intron	N/A	ENSP00000467537.1
	PTPRS	ENST00000588012.5	TSL:1	c.569-3368C>T		intron	N/A	ENSP00000465443.1

Frequencies

GnomAD3 genomes AF: 0.564 AC: 85672 AN: 151876 Hom.: 26641 Cov.: 32

Gnomad AFR AF: 0.285

Gnomad AMI AF: 0.749

Gnomad AMR AF: 0.701

Gnomad ASJ AF: 0.646

Gnomad EAS AF: 0.806

Gnomad SAS AF: 0.603

Gnomad FIN AF: 0.544

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.677

Gnomad OTH AF: 0.604

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.564 AC: 85677 AN: 151994 Hom.: 26637 Cov.: 32 AF XY: 0.562 AC XY: 41781 AN XY: 74314

African (AFR) AF: 0.285 AC: 11792 AN: 41434

American (AMR) AF: 0.701 AC: 10709 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.646 AC: 2240 AN: 3468

East Asian (EAS) AF: 0.807 AC: 4161 AN: 5154

South Asian (SAS) AF: 0.603 AC: 2908 AN: 4820

European-Finnish (FIN) AF: 0.544 AC: 5751 AN: 10572

Middle Eastern (MID) AF: 0.619 AC: 182 AN: 294

European-Non Finnish (NFE) AF: 0.677 AC: 45982 AN: 67942

Other (OTH) AF: 0.601 AC: 1269 AN: 2112

Alfa AF: 0.629 Hom.: 16429

Bravo AF: 0.567

Asia WGS AF: 0.656 AC: 2280 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.6
DANN	Benign	0.63
PhyloP100		0.70
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: rs2238640; hg19: chr19-5261506;