9-8331644-G-A

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_002839.4(PTPRD):c.5472C>T(p.Ile1824=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00217 in 1,613,714 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0014 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0023 (7 hom.)
• Consequence: PTPRD NM_002839.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.86

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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP6: Variant 9-8331644-G-A is Benign according to our data. Variant chr9-8331644-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 734322.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.87 with no splicing effect.
• BS2: High AC in GnomAd at 217 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTPRD	NM_002839.4	c.5472C>T	p.Ile1824=	synonymous_variant	44/46	ENST00000381196.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTPRD	ENST00000381196.9	c.5472C>T	p.Ile1824=	synonymous_variant	44/46	5	NM_002839.4	P1

Frequencies

GnomAD3 genomes AF: 0.00143 AC: 217 AN: 151880 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000920

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000394

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.000284

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00231

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.00148 AC: 371 AN: 250524 Hom.: 1 AF XY: 0.00145 AC XY: 196 AN XY: 135418

Gnomad AFR exome AF: 0.000555

Gnomad AMR exome AF: 0.000522

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000653

Gnomad SAS exome AF: 0.00105

Gnomad FIN exome AF: 0.000462

Gnomad NFE exome AF: 0.00250

Gnomad OTH exome AF: 0.00115

GnomAD4 exome AF: 0.00225 AC: 3293 AN: 1461714 Hom.: 7 Cov.: 33 AF XY: 0.00222 AC XY: 1617 AN XY: 727158

Gnomad4 AFR exome AF: 0.000657

Gnomad4 AMR exome AF: 0.000403

Gnomad4 ASJ exome AF: 0.0000765

Gnomad4 EAS exome AF: 0.000454

Gnomad4 SAS exome AF: 0.00122

Gnomad4 FIN exome AF: 0.000599

Gnomad4 NFE exome AF: 0.00268

Gnomad4 OTH exome AF: 0.00164

GnomAD4 genome AF: 0.00142 AC: 216 AN: 152000 Hom.: 0 Cov.: 33 AF XY: 0.00113 AC XY: 84 AN XY: 74298

Gnomad4 AFR AF: 0.000894

Gnomad4 AMR AF: 0.000393

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00136

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.000284

Gnomad4 NFE AF: 0.00231

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.00176 Hom.: 1

Bravo AF: 0.00139

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.00224

EpiControl AF: 0.00279

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Oct 19, 2018	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2022	PTPRD: BP4, BP7 -

PTPRD-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 15, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
Cadd	Benign	5.4
Dann	Benign	0.67

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: rs140620944; hg19: chr9-8331644; COSMIC: COSV61952981;