4-54285924-AGACATCATGCATGA-AGA

Position:

• chr4-54285924-AGACATCATGCATGA-AGA

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2 PM4 PP3

The NM_006206.6(PDGFRA):​c.2526_2537delCATCATGCATGA​(p.Ile843_Asp846del) variant causes a disruptive inframe deletion change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: PDGFRA NM_006206.6 disruptive_inframe_deletion
• Clinical Significance: Conflicting classifications of pathogenicity no assertion criteria provided P:1 U:1
• Conservation: PhyloP100: 10.0

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]

ENSG00000282278 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_006206.6.
• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDGFRA	NM_006206.6	c.2526_2537delCATCATGCATGA	p.Ile843_Asp846del	disruptive_inframe_deletion	18/23	ENST00000257290.10	NP_006197.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDGFRA	ENST00000257290.10	c.2526_2537delCATCATGCATGA	p.Ile843_Asp846del	disruptive_inframe_deletion	18/23	1	NM_006206.6	ENSP00000257290.5
ENSG00000282278	ENST00000507166.5	c.1806_1817delCATCATGCATGA	p.Ile603_Asp606del	disruptive_inframe_deletion	19/24	2		ENSP00000423325.1

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Pathogenic:1 Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Gastrointestinal stromal tumor Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jan 31, 2003

- -

not provided Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

Department of Pathology and Laboratory Medicine, Sinai Health System

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- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1553906053; hg19: chr4-55152091;