9-10487877-T-A

Variant names:

• chr9-10487877-T-A
• rs2484741
• NM_002839.4:c.-600+124521A>T

Variant summary

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

The NM_002839.4(PTPRD):​c.-600+124521A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.747 in 151,028 control chromosomes in the GnomAD database, including 42,486 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 0.75 (42486 hom., cov: 27)
• Consequence: PTPRD NM_002839.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.19
• Publications: 1 publications found

Genes affected

PTPRD (HGNC:9668): (protein tyrosine phosphatase receptor type D) 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 three Ig-like and eight fibronectin type III-like domains. Studies of the similar genes in chicken and fly suggest the role of this PTP is in promoting neurite growth, and regulating neurons axon guidance. Multiple alternatively spliced transcript variants of this gene have been reported. A related pseudogene has been identified on chromosome 5. [provided by RefSeq, Jan 2010]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.808 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRD	NM_002839.4	c.-600+124521A>T		intron_variant	Intron 2 of 45	ENST00000381196.9	NP_002830.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPRD	ENST00000381196.9	c.-600+124521A>T		intron_variant	Intron 2 of 45	5	NM_002839.4	ENSP00000370593.3
PTPRD	ENST00000463477.5	c.-672+124521A>T		intron_variant	Intron 2 of 16	1		ENSP00000417661.1
PTPRD	ENST00000850942.1	c.-761+124521A>T		intron_variant	Intron 2 of 47			ENSP00000521027.1

Frequencies

GnomAD3 genomes AF: 0.747 AC: 112799 AN: 150910 Hom.: 42449 Cov.: 27

Gnomad AFR AF: 0.815

Gnomad AMI AF: 0.753

Gnomad AMR AF: 0.701

Gnomad ASJ AF: 0.702

Gnomad EAS AF: 0.590

Gnomad SAS AF: 0.676

Gnomad FIN AF: 0.757

Gnomad MID AF: 0.618

Gnomad NFE AF: 0.737

Gnomad OTH AF: 0.707

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

GnomAD4 genome AF: 0.747 AC: 112889 AN: 151028 Hom.: 42486 Cov.: 27 AF XY: 0.746 AC XY: 54932 AN XY: 73674

African (AFR) AF: 0.815 AC: 33513 AN: 41114

American (AMR) AF: 0.700 AC: 10616 AN: 15172

Ashkenazi Jewish (ASJ) AF: 0.702 AC: 2431 AN: 3462

East Asian (EAS) AF: 0.590 AC: 3004 AN: 5094

South Asian (SAS) AF: 0.677 AC: 3232 AN: 4774

European-Finnish (FIN) AF: 0.757 AC: 7789 AN: 10294

Middle Eastern (MID) AF: 0.603 AC: 176 AN: 292

European-Non Finnish (NFE) AF: 0.737 AC: 49960 AN: 67820

Other (OTH) AF: 0.708 AC: 1483 AN: 2096

Alfa AF: 0.660 Hom.: 1930

Bravo AF: 0.744

Asia WGS AF: 0.657 AC: 2277 AN: 3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.0
DANN	Benign	0.16
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2484741; hg19: chr9-10487877; COSMIC: COSV71789264;