Genetic Variant NM_006206.6:c.577G>T (chr4-54263876-G-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_006206.6(PDGFRA):c.577G>T(p.Val193Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V193I) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Consequence

PDGFRA
NM_006206.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.09

Publications

0 publications found

Variant links:

Genes affected

PDGFRA (HGNC:8803): (platelet derived growth factor receptor alpha) This gene encodes a cell surface tyrosine kinase receptor for members of the platelet-derived growth factor family. These growth factors are mitogens for cells of mesenchymal origin. The identity of the growth factor bound to a receptor monomer determines whether the functional receptor is a homodimer or a heterodimer, composed of both platelet-derived growth factor receptor alpha and beta polypeptides. Studies suggest that this gene plays a role in organ development, wound healing, and tumor progression. Mutations in this gene have been associated with idiopathic hypereosinophilic syndrome, somatic and familial gastrointestinal stromal tumors, and a variety of other cancers. [provided by RefSeq, Mar 2012]

PDGFRA Gene-Disease associations (from GenCC):

gastrointestinal stromal tumor
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae)
polyps, multiple and recurrent inflammatory fibroid, gastrointestinal
Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Genomics England PanelApp, Ambry Genetics, G2P
congenital heart disease
Inheritance: AD Classification: LIMITED Submitted by: ClinGen
isolated cleft palate
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

PDGFRA links:

ENSG00000282278 (HGNC:):

ENSG00000282278 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006206.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
PDGFRA	NM_006206.6	MANE Select	c.577G>T	p.Val193Phe	missense	Exon 4 of 23	NP_006197.1
PDGFRA	NM_001347828.2		c.652G>T	p.Val218Phe	missense	Exon 5 of 24	NP_001334757.1
PDGFRA	NM_001347830.2		c.616G>T	p.Val206Phe	missense	Exon 4 of 23	NP_001334759.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
PDGFRA	ENST00000257290.10	TSL:1 MANE Select	c.577G>T	p.Val193Phe	missense	Exon 4 of 23	ENSP00000257290.5
PDGFRA	ENST00000508170.5	TSL:1	c.577G>T	p.Val193Phe	missense	Exon 4 of 4	ENSP00000425648.1
PDGFRA	ENST00000509092.5	TSL:1	n.395G>T		non_coding_transcript_exon	Exon 3 of 15

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.098

BayesDel_noAF

Benign

-0.38

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.24

Eigen

Benign

0.0048

Eigen_PC

Benign

-0.13

FATHMM_MKL

Benign

0.40

LIST_S2

Benign

0.76

M_CAP

Benign

0.018

MetaRNN

Uncertain

0.44

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.7

PhyloP100

1.1

PrimateAI

Benign

0.46

PROVEAN

Benign

-1.9

REVEL

Benign

0.14

Sift

Uncertain

0.012

Sift4G

Uncertain

0.049

Polyphen

0.98

Vest4

0.52

MutPred

0.40

Gain of sheet (P = 0.1451)

MVP

0.60

MPC

0.88

ClinPred

0.79

GERP RS

2.5

Varity_R

0.16

gMVP

0.91

Mutation Taster

=75/25

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over