rs2242148

chr18-8361187-A-G

Variant summary

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

The NM_001105244.2(PTPRM):c.3055-9703A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.232 in 152,010 control chromosomes in the GnomAD database, including 4,851 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 0.23 (4850 hom., cov: 32)
  • Exomes 𝑓: 0.20 (1 hom.)
• Consequence: PTPRM NM_001105244.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.292

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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.31 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTPRM	NM_001105244.2	c.3055-9703A>G		intron_variant		ENST00000580170.6
LOC100192426	NR_024419.1	n.345-96T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTPRM	ENST00000580170.6	c.3055-9703A>G		intron_variant		1	NM_001105244.2	A1
	ENST00000580491.1	n.345-96T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.232 AC: 35194 AN: 151870 Hom.: 4847 Cov.: 32

Gnomad AFR AF: 0.0901

Gnomad AMI AF: 0.278

Gnomad AMR AF: 0.218

Gnomad ASJ AF: 0.285

Gnomad EAS AF: 0.124

Gnomad SAS AF: 0.168

Gnomad FIN AF: 0.338

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.314

Gnomad OTH AF: 0.224

GnomAD4 exome AF: 0.200 AC: 4 AN: 20 Hom.: 1 AF XY: 0.214 AC XY: 3 AN XY: 14

Gnomad4 ASJ exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.286

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.232 AC: 35193 AN: 151990 Hom.: 4850 Cov.: 32 AF XY: 0.230 AC XY: 17119 AN XY: 74282

Gnomad4 AFR AF: 0.0898

Gnomad4 AMR AF: 0.218

Gnomad4 ASJ AF: 0.285

Gnomad4 EAS AF: 0.123

Gnomad4 SAS AF: 0.168

Gnomad4 FIN AF: 0.338

Gnomad4 NFE AF: 0.314

Gnomad4 OTH AF: 0.222

Alfa AF: 0.288 Hom.: 8633

Bravo AF: 0.221

Asia WGS AF: 0.128 AC: 445 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	7.0
Dann	Benign	0.65

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs2242148; hg19: chr18-8361185;