rs2412559

chr4-54285544-C-Achr4-54285544-C-Gchr4-54285544-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_006206.6(PDGFRA):c.2439+58C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.988 in 825,408 control chromosomes in the GnomAD database, including 403,041 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.96 (70226 hom., cov: 31)
  • Exomes 𝑓: 0.99 (332815 hom.)
• Consequence: PDGFRA NM_006206.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0460

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 4-54285544-C-A is Benign according to our data. Variant chr4-54285544-C-A is described in ClinVar as [Benign]. Clinvar id is 1234478.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDGFRA	NM_006206.6	c.2439+58C>A		intron_variant		ENST00000257290.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDGFRA	ENST00000257290.10	c.2439+58C>A		intron_variant		1	NM_006206.6	P1

Frequencies

GnomAD3 genomes AF: 0.959 AC: 145844 AN: 152104 Hom.: 70201 Cov.: 31

Gnomad AFR AF: 0.859

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.982

Gnomad ASJ AF: 0.999

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.999

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.987

Gnomad NFE AF: 0.999

Gnomad OTH AF: 0.970

GnomAD4 exome AF: 0.994 AC: 669203 AN: 673186 Hom.: 332815 AF XY: 0.995 AC XY: 362171 AN XY: 363934

Gnomad4 AFR exome AF: 0.858

Gnomad4 AMR exome AF: 0.990

Gnomad4 ASJ exome AF: 0.999

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.999

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.999

Gnomad4 OTH exome AF: 0.987

GnomAD4 genome AF: 0.959 AC: 145923 AN: 152222 Hom.: 70226 Cov.: 31 AF XY: 0.960 AC XY: 71489 AN XY: 74446

Gnomad4 AFR AF: 0.858

Gnomad4 AMR AF: 0.982

Gnomad4 ASJ AF: 0.999

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.999

Gnomad4 FIN AF: 1.00

Gnomad4 NFE AF: 0.999

Gnomad4 OTH AF: 0.968

Alfa AF: 0.994 Hom.: 127365

Bravo AF: 0.953

Asia WGS AF: 0.976 AC: 3395 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 22, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	2.5
Dann	Benign	0.60

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: rs2412559; hg19: chr4-55151711; COSMIC: COSV99955340; COSMIC: COSV99955340;