rs4626664

Variant names:

• chr9-9261737-G-A
• rs4626664
• NM_002839.4:c.-202-78374C>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.-202-78374C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 151,442 control chromosomes in the GnomAD database, including 3,383 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 0.20 (3383 hom., cov: 31)
• Consequence: PTPRD NM_002839.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.360
• Publications: 37 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.39 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRD	NM_002839.4	c.-202-78374C>T		intron_variant	Intron 9 of 45	ENST00000381196.9	NP_002830.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPRD	ENST00000381196.9	c.-202-78374C>T		intron_variant	Intron 9 of 45	5	NM_002839.4	ENSP00000370593.3
PTPRD	ENST00000463477.5	c.-202-78374C>T		intron_variant	Intron 10 of 16	1		ENSP00000417661.1
PTPRD	ENST00000850942.1	c.-202-78374C>T		intron_variant	Intron 11 of 47			ENSP00000521027.1

Frequencies

GnomAD3 genomes AF: 0.200 AC: 30279 AN: 151324 Hom.: 3376 Cov.: 31

Gnomad AFR AF: 0.260

Gnomad AMI AF: 0.204

Gnomad AMR AF: 0.235

Gnomad ASJ AF: 0.123

Gnomad EAS AF: 0.404

Gnomad SAS AF: 0.223

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.150

Gnomad OTH AF: 0.179

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

GnomAD4 genome AF: 0.200 AC: 30302 AN: 151442 Hom.: 3383 Cov.: 31 AF XY: 0.203 AC XY: 14987 AN XY: 74002

African (AFR) AF: 0.260 AC: 10730 AN: 41314

American (AMR) AF: 0.235 AC: 3568 AN: 15174

Ashkenazi Jewish (ASJ) AF: 0.123 AC: 425 AN: 3468

East Asian (EAS) AF: 0.404 AC: 2046 AN: 5062

South Asian (SAS) AF: 0.223 AC: 1070 AN: 4802

European-Finnish (FIN) AF: 0.162 AC: 1708 AN: 10534

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.150 AC: 10162 AN: 67772

Other (OTH) AF: 0.182 AC: 384 AN: 2110

Alfa AF: 0.169 Hom.: 9599

Bravo AF: 0.210

Asia WGS AF: 0.305 AC: 1057 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.4
DANN	Benign	0.67
PhyloP100		-0.36
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: rs4626664; hg19: chr9-9261737;