9-9572790-T-G

Variant names:

• chr9-9572790-T-G
• rs638230
• NM_002839.4:c.-237+1942A>C

Variant summary

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

The NM_002839.4(PTPRD):​c.-237+1942A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.25 in 150,904 control chromosomes in the GnomAD database, including 5,428 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 0.25 (5428 hom., cov: 30)
• Consequence: PTPRD NM_002839.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.338
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.319 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRD	NM_002839.4	c.-237+1942A>C		intron_variant	Intron 8 of 45	ENST00000381196.9	NP_002830.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPRD	ENST00000381196.9	c.-237+1942A>C		intron_variant	Intron 8 of 45	5	NM_002839.4	ENSP00000370593.3
PTPRD	ENST00000463477.5	c.-309+1942A>C		intron_variant	Intron 8 of 16	1		ENSP00000417661.1
PTPRD	ENST00000850942.1	c.-237+1942A>C		intron_variant	Intron 10 of 47			ENSP00000521027.1

Frequencies

GnomAD3 genomes AF: 0.250 AC: 37705 AN: 150802 Hom.: 5426 Cov.: 30

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.407

Gnomad AMR AF: 0.240

Gnomad ASJ AF: 0.302

Gnomad EAS AF: 0.195

Gnomad SAS AF: 0.126

Gnomad FIN AF: 0.389

Gnomad MID AF: 0.255

Gnomad NFE AF: 0.323

Gnomad OTH AF: 0.269

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

GnomAD4 genome AF: 0.250 AC: 37713 AN: 150904 Hom.: 5428 Cov.: 30 AF XY: 0.250 AC XY: 18457 AN XY: 73706

African (AFR) AF: 0.112 AC: 4641 AN: 41334

American (AMR) AF: 0.240 AC: 3620 AN: 15104

Ashkenazi Jewish (ASJ) AF: 0.302 AC: 1045 AN: 3462

East Asian (EAS) AF: 0.195 AC: 999 AN: 5124

South Asian (SAS) AF: 0.127 AC: 609 AN: 4812

European-Finnish (FIN) AF: 0.389 AC: 4054 AN: 10428

Middle Eastern (MID) AF: 0.243 AC: 71 AN: 292

European-Non Finnish (NFE) AF: 0.323 AC: 21730 AN: 67336

Other (OTH) AF: 0.273 AC: 574 AN: 2104

Alfa AF: 0.272 Hom.: 3284

Bravo AF: 0.236

Asia WGS AF: 0.181 AC: 628 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.54
DANN	Benign	0.58
PhyloP100		-0.34
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: rs638230; hg19: chr9-9572790; COSMIC: COSV67064811;