rs657849

Variant names:

• chr9-9593722-C-A
• rs657849
• NM_002839.4:c.-286-18941G>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.-286-18941G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.257 in 151,826 control chromosomes in the GnomAD database, including 6,008 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 0.26 (6008 hom., cov: 31)
• Consequence: PTPRD NM_002839.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.00
• Publications: 3 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=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.342 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRD	NM_002839.4	c.-286-18941G>T		intron_variant	Intron 7 of 45	ENST00000381196.9	NP_002830.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPRD	ENST00000381196.9	c.-286-18941G>T		intron_variant	Intron 7 of 45	5	NM_002839.4	ENSP00000370593.3
PTPRD	ENST00000463477.5	c.-358-18941G>T		intron_variant	Intron 7 of 16	1		ENSP00000417661.1
PTPRD	ENST00000850942.1	c.-286-18941G>T		intron_variant	Intron 9 of 47			ENSP00000521027.1

Frequencies

GnomAD3 genomes AF: 0.257 AC: 38960 AN: 151708 Hom.: 6004 Cov.: 31

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.366

Gnomad AMR AF: 0.217

Gnomad ASJ AF: 0.283

Gnomad EAS AF: 0.184

Gnomad SAS AF: 0.139

Gnomad FIN AF: 0.398

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.346

Gnomad OTH AF: 0.274

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

GnomAD4 genome AF: 0.257 AC: 38984 AN: 151826 Hom.: 6008 Cov.: 31 AF XY: 0.257 AC XY: 19038 AN XY: 74184

African (AFR) AF: 0.106 AC: 4413 AN: 41484

American (AMR) AF: 0.217 AC: 3293 AN: 15186

Ashkenazi Jewish (ASJ) AF: 0.283 AC: 979 AN: 3464

East Asian (EAS) AF: 0.184 AC: 942 AN: 5128

South Asian (SAS) AF: 0.139 AC: 668 AN: 4816

European-Finnish (FIN) AF: 0.398 AC: 4203 AN: 10556

Middle Eastern (MID) AF: 0.234 AC: 68 AN: 290

European-Non Finnish (NFE) AF: 0.346 AC: 23499 AN: 67882

Other (OTH) AF: 0.278 AC: 585 AN: 2108

Alfa AF: 0.298 Hom.: 1146

Bravo AF: 0.237

Asia WGS AF: 0.186 AC: 647 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.46
DANN	Benign	0.11
PhyloP100		-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: rs657849; hg19: chr9-9593722; COSMIC: COSV67064983;