rs2290819

Positions:

• chr18-8364964-G-T

Variant summary

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

The NM_001105244.2(PTPRM):​c.3055-5926G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.435 in 151,982 control chromosomes in the GnomAD database, including 14,979 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 0.44 (14964 hom., cov: 32)
  • Exomes 𝑓: 0.62 (15 hom.)
• Consequence: PTPRM NM_001105244.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.109

Genes affected

PTPRM (HGNC:9675): (protein tyrosine phosphatase receptor type M) 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 possesses an extracellular region, a single transmembrane region, and two tandem catalytic domains, and thus represents a receptor-type PTP. The extracellular region contains a meprin-A5 antigen-PTP mu (MAM) domain, an Ig-like domain and four fibronectin type III-like repeats. This PTP has been shown to mediate cell-cell aggregation through the interaction with another molecule of this PTP on an adjacent cell. This PTP can interact with scaffolding protein RACK1/GNB2L1, which may be necessary for the downstream signaling in response to cell-cell adhesion. Alternative splicing results in multiple transcripts encoding distinct isoforms. [provided by RefSeq, Jul 2008]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.556 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTPRM	NM_001105244.2	c.3055-5926G>T		intron_variant		ENST00000580170.6
LOC100192426	NR_024419.1	n.289C>A		non_coding_transcript_exon_variant	3/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTPRM	ENST00000580170.6	c.3055-5926G>T		intron_variant		1	NM_001105244.2	A1
	ENST00000580491.1	n.289C>A		non_coding_transcript_exon_variant	3/4	2

Frequencies

GnomAD3 genomes AF: 0.435 AC: 66062 AN: 151796 Hom.: 14944 Cov.: 32

Gnomad AFR AF: 0.562

Gnomad AMI AF: 0.360

Gnomad AMR AF: 0.343

Gnomad ASJ AF: 0.326

Gnomad EAS AF: 0.308

Gnomad SAS AF: 0.462

Gnomad FIN AF: 0.425

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.395

Gnomad OTH AF: 0.438

GnomAD4 exome AF: 0.618 AC: 42 AN: 68 Hom.: 15 Cov.: 0 AF XY: 0.500 AC XY: 17 AN XY: 34

Gnomad4 AFR exome AF: 0.500

Gnomad4 EAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.795

Gnomad4 NFE exome AF: 0.250

GnomAD4 genome AF: 0.435 AC: 66132 AN: 151914 Hom.: 14964 Cov.: 32 AF XY: 0.432 AC XY: 32110 AN XY: 74260

Gnomad4 AFR AF: 0.562

Gnomad4 AMR AF: 0.342

Gnomad4 ASJ AF: 0.326

Gnomad4 EAS AF: 0.308

Gnomad4 SAS AF: 0.462

Gnomad4 FIN AF: 0.425

Gnomad4 NFE AF: 0.395

Gnomad4 OTH AF: 0.438

Alfa AF: 0.410 Hom.: 2623

Bravo AF: 0.430

Asia WGS AF: 0.410 AC: 1427 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.2
DANN	Benign	0.52

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: rs2290819; hg19: chr18-8364962;