rs2279776

Variant names:

• chr9-8389364-C-G
• rs2279776
• NM_002839.4:c.4254G>C

Your query was ambiguous. Multiple possible variants found:

• chr9-8389364-C-G
• chr9-8389364-C-T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_002839.4(PTPRD):​c.4254G>C​(p.Gly1418Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.453 in 1,611,518 control chromosomes in the GnomAD database, including 168,428 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.50 (19402 hom., cov: 31)
  • Exomes 𝑓: 0.45 (149026 hom.)
• Consequence: PTPRD NM_002839.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.274
• Publications: 28 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP6: Variant 9-8389364-C-G is Benign according to our data. Variant chr9-8389364-C-G is described in ClinVar as Benign. ClinVar VariationId is 1225000.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.274 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.64 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRD	NM_002839.4	c.4254G>C	p.Gly1418Gly	synonymous_variant	Exon 37 of 46	ENST00000381196.9	NP_002830.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPRD	ENST00000381196.9	c.4254G>C	p.Gly1418Gly	synonymous_variant	Exon 37 of 46	5	NM_002839.4	ENSP00000370593.3

Frequencies

GnomAD3 genomes AF: 0.498 AC: 75512 AN: 151622 Hom.: 19374 Cov.: 31

Gnomad AFR AF: 0.582

Gnomad AMI AF: 0.641

Gnomad AMR AF: 0.489

Gnomad ASJ AF: 0.464

Gnomad EAS AF: 0.659

Gnomad SAS AF: 0.566

Gnomad FIN AF: 0.492

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.433

Gnomad OTH AF: 0.486

GnomAD2 exomes AF: 0.495 AC: 123709 AN: 249724 AF XY: 0.496

Gnomad AFR exome AF: 0.585

Gnomad AMR exome AF: 0.490

Gnomad ASJ exome AF: 0.460

Gnomad EAS exome AF: 0.673

Gnomad FIN exome AF: 0.490

Gnomad NFE exome AF: 0.442

Gnomad OTH exome AF: 0.472

GnomAD4 exome AF: 0.448 AC: 654647 AN: 1459778 Hom.: 149026 Cov.: 37 AF XY: 0.451 AC XY: 327711 AN XY: 726250

African (AFR) AF: 0.590 AC: 19660 AN: 33328

American (AMR) AF: 0.489 AC: 21819 AN: 44584

Ashkenazi Jewish (ASJ) AF: 0.460 AC: 11979 AN: 26062

East Asian (EAS) AF: 0.619 AC: 24493 AN: 39598

South Asian (SAS) AF: 0.553 AC: 47526 AN: 86016

European-Finnish (FIN) AF: 0.491 AC: 26185 AN: 53354

Middle Eastern (MID) AF: 0.516 AC: 2974 AN: 5762

European-Non Finnish (NFE) AF: 0.425 AC: 471861 AN: 1110742

Other (OTH) AF: 0.467 AC: 28150 AN: 60332

GnomAD4 genome AF: 0.498 AC: 75602 AN: 151740 Hom.: 19402 Cov.: 31 AF XY: 0.505 AC XY: 37426 AN XY: 74174

African (AFR) AF: 0.583 AC: 24097 AN: 41368

American (AMR) AF: 0.490 AC: 7459 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.464 AC: 1608 AN: 3466

East Asian (EAS) AF: 0.659 AC: 3390 AN: 5146

South Asian (SAS) AF: 0.565 AC: 2722 AN: 4818

European-Finnish (FIN) AF: 0.492 AC: 5188 AN: 10538

Middle Eastern (MID) AF: 0.517 AC: 152 AN: 294

European-Non Finnish (NFE) AF: 0.433 AC: 29374 AN: 67870

Other (OTH) AF: 0.488 AC: 1029 AN: 2110

Alfa AF: 0.448 Hom.: 5123

Bravo AF: 0.502

Asia WGS AF: 0.599 AC: 2081 AN: 3476

EpiCase AF: 0.440

EpiControl AF: 0.442

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Oct 22, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	3.5
DANN	Benign	0.70
PhyloP100		0.27
Mutation Taster		=76/24	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: rs2279776; hg19: chr9-8389364; COSMIC: COSV61928282;