9-10505224-C-T

Variant names:

• chr9-10505224-C-T
• rs72700966
• NM_002839.4:c.-600+107174G>A

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+107174G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0987 in 152,188 control chromosomes in the GnomAD database, including 1,004 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 0.099 (1004 hom., cov: 33)
• Consequence: PTPRD NM_002839.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.119
• Publications: 7 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.174 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRD	NM_002839.4	c.-600+107174G>A		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+107174G>A		intron_variant	Intron 2 of 45	5	NM_002839.4	ENSP00000370593.3
PTPRD	ENST00000463477.5	c.-672+107174G>A		intron_variant	Intron 2 of 16	1		ENSP00000417661.1
PTPRD	ENST00000850942.1	c.-761+107174G>A		intron_variant	Intron 2 of 47			ENSP00000521027.1

Frequencies

GnomAD3 genomes AF: 0.0987 AC: 15012 AN: 152070 Hom.: 1002 Cov.: 33

Gnomad AFR AF: 0.178

Gnomad AMI AF: 0.133

Gnomad AMR AF: 0.0559

Gnomad ASJ AF: 0.0830

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0230

Gnomad FIN AF: 0.0662

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0789

Gnomad OTH AF: 0.0861

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

GnomAD4 genome AF: 0.0987 AC: 15028 AN: 152188 Hom.: 1004 Cov.: 33 AF XY: 0.0955 AC XY: 7108 AN XY: 74410

African (AFR) AF: 0.178 AC: 7378 AN: 41520

American (AMR) AF: 0.0558 AC: 853 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0830 AC: 288 AN: 3470

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5180

South Asian (SAS) AF: 0.0228 AC: 110 AN: 4820

European-Finnish (FIN) AF: 0.0662 AC: 701 AN: 10594

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0789 AC: 5365 AN: 68008

Other (OTH) AF: 0.0862 AC: 182 AN: 2112

Alfa AF: 0.0640 Hom.: 136

Bravo AF: 0.103

Asia WGS AF: 0.0210 AC: 73 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.9
DANN	Benign	0.38
PhyloP100		0.12
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: rs72700966; hg19: chr9-10505224;