9-8926956-T-C

Variant names:

• chr9-8926956-T-C
• rs1897676
• NM_002839.4:c.-104+91741A>G

Variant summary

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

The NM_002839.4(PTPRD):​c.-104+91741A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.496 in 151,936 control chromosomes in the GnomAD database, including 19,349 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 0.50 (19349 hom., cov: 32)
• Consequence: PTPRD NM_002839.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00100
• Publications: 4 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.79 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002839.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRD	NM_002839.4	MANE Select	c.-104+91741A>G		intron	N/A	NP_002830.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRD	ENST00000381196.9	TSL:5 MANE Select	c.-104+91741A>G		intron	N/A	ENSP00000370593.3
	PTPRD	ENST00000463477.5	TSL:1	c.-104+91741A>G		intron	N/A	ENSP00000417661.1
	PTPRD	ENST00000850942.1		c.-104+91741A>G		intron	N/A	ENSP00000521027.1

Frequencies

GnomAD3 genomes AF: 0.496 AC: 75283 AN: 151818 Hom.: 19325 Cov.: 32

Gnomad AFR AF: 0.527

Gnomad AMI AF: 0.475

Gnomad AMR AF: 0.631

Gnomad ASJ AF: 0.513

Gnomad EAS AF: 0.810

Gnomad SAS AF: 0.464

Gnomad FIN AF: 0.478

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.428

Gnomad OTH AF: 0.471

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

GnomAD4 genome AF: 0.496 AC: 75359 AN: 151936 Hom.: 19349 Cov.: 32 AF XY: 0.503 AC XY: 37350 AN XY: 74244

African (AFR) AF: 0.527 AC: 21819 AN: 41428

American (AMR) AF: 0.632 AC: 9634 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.513 AC: 1780 AN: 3470

East Asian (EAS) AF: 0.810 AC: 4180 AN: 5158

South Asian (SAS) AF: 0.465 AC: 2234 AN: 4806

European-Finnish (FIN) AF: 0.478 AC: 5045 AN: 10546

Middle Eastern (MID) AF: 0.500 AC: 147 AN: 294

European-Non Finnish (NFE) AF: 0.428 AC: 29093 AN: 67964

Other (OTH) AF: 0.472 AC: 995 AN: 2110

Alfa AF: 0.455 Hom.: 52870

Bravo AF: 0.517

Asia WGS AF: 0.615 AC: 2136 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	7.3
DANN	Benign	0.82
PhyloP100		0.0010
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: rs1897676; hg19: chr9-8926956;