NM_006206.6(PDGFRA):c.764G>C (p.Gly255Ala) AND Gastrointestinal stromal tumor

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Mar 29, 2023
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV003841643.2

Allele description [Variation Report for NM_006206.6(PDGFRA):c.764G>C (p.Gly255Ala)]

NM_006206.6(PDGFRA):c.764G>C (p.Gly255Ala)

Gene:

PDGFRA:platelet derived growth factor receptor alpha [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

4q12

Genomic location:

Preferred name:

NM_006206.6(PDGFRA):c.764G>C (p.Gly255Ala)

HGVS:

NC_000004.12:g.54267293G>C
NG_009250.1:g.43197G>C
NM_001347827.2:c.764G>C
NM_001347828.2:c.839G>C
NM_001347829.2:c.764G>C
NM_001347830.2:c.803G>C
NM_006206.6:c.764G>CMANE SELECT
NP_001334756.1:p.Gly255Ala
NP_001334757.1:p.Gly280Ala
NP_001334758.1:p.Gly255Ala
NP_001334759.1:p.Gly268Ala
NP_006197.1:p.Gly255Ala
NP_006197.1:p.Gly255Ala
LRG_309t1:c.764G>C
LRG_309:g.43197G>C
LRG_309p1:p.Gly255Ala
NC_000004.11:g.55133460G>C
NM_006206.4:c.764G>C

Protein change:

G255A

Molecular consequence:

NM_001347827.2:c.764G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001347828.2:c.839G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001347829.2:c.764G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001347830.2:c.803G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_006206.6:c.764G>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Gastrointestinal stromal tumor
Synonyms:: Gastrointestinal Stromal Sarcoma; Gastrointestinal stromal tumor, somatic; Gastrointestinal stroma tumor
Identifiers:: MONDO: MONDO:0011719; MeSH: D046152; MedGen: C0238198; Orphanet: 44890; OMIM: 606764; Human Phenotype Ontology: HP:0100723

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RNA Interference
A gene silencing phenomenon whereby specific dsRNAs (RNA, DOUBLE-STRANDED) trigger the degradation of homologous mRNA (RNA, MESSENGER). The specific dsRNAs are processed into ...<br/>Year introduced: 2003

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004648722	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Mar 29, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004648722

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Mar 29, 2023)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004648722.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt PDGFRA protein function. This variant has not been reported in the literature in individuals affected with PDGFRA-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 255 of the PDGFRA protein (p.Gly255Ala).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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