rs1975197

Positions:

• chr9-8846955-G-A

Variant summary

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

The NM_002839.4(PTPRD):​c.-103-113009C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 151,970 control chromosomes in the GnomAD database, including 2,187 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 0.16 (2187 hom., cov: 32)
• Consequence: PTPRD NM_002839.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.213

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.3 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTPRD	NM_002839.4	c.-103-113009C>T		intron_variant		ENST00000381196.9	NP_002830.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTPRD	ENST00000381196.9	c.-103-113009C>T		intron_variant		5	NM_002839.4	ENSP00000370593	P1
PTPRD	ENST00000463477.5	c.-103-113009C>T		intron_variant		1		ENSP00000417661
PTPRD	ENST00000481079.1	c.-104+10683C>T		intron_variant		2		ENSP00000417890

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24446 AN: 151852 Hom.: 2188 Cov.: 32

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.0538

Gnomad AMR AF: 0.222

Gnomad ASJ AF: 0.0892

Gnomad EAS AF: 0.313

Gnomad SAS AF: 0.234

Gnomad FIN AF: 0.112

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.162

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

GnomAD4 genome AF: 0.161 AC: 24466 AN: 151970 Hom.: 2187 Cov.: 32 AF XY: 0.162 AC XY: 12022 AN XY: 74278

Gnomad4 AFR AF: 0.115

Gnomad4 AMR AF: 0.222

Gnomad4 ASJ AF: 0.0892

Gnomad4 EAS AF: 0.313

Gnomad4 SAS AF: 0.233

Gnomad4 FIN AF: 0.112

Gnomad4 NFE AF: 0.171

Gnomad4 OTH AF: 0.164

Alfa AF: 0.171 Hom.: 5159

Bravo AF: 0.167

Asia WGS AF: 0.258 AC: 898 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.7
DANN	Benign	0.51

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

Publications

LitVar

Other links and lift over

dbSNP: rs1975197; hg19: chr9-8846955;