rs2412559

Variant names:

• chr4-54285544-C-A
• rs2412559
• NM_006206.6:c.2439+58C>A

Your query was ambiguous. Multiple possible variants found:

• chr4-54285544-C-A
• chr4-54285544-C-G
• chr4-54285544-C-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0460
• Publications: 9 publications found

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)

ENSG00000282278 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 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 VariationId is 1234478.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDGFRA	NM_006206.6	MANE Select	c.2439+58C>A		intron	N/A	NP_006197.1
	PDGFRA	NM_001347828.2		c.2514+58C>A		intron	N/A	NP_001334757.1
	PDGFRA	NM_001347830.2		c.2478+58C>A		intron	N/A	NP_001334759.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDGFRA	ENST00000257290.10	TSL:1 MANE Select	c.2439+58C>A		intron	N/A	ENSP00000257290.5
	ENSG00000282278	ENST00000507166.5	TSL:2	c.1719+58C>A		intron	N/A	ENSP00000423325.1

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

African (AFR) AF: 0.858 AC: 15822 AN: 18442

American (AMR) AF: 0.990 AC: 43035 AN: 43466

Ashkenazi Jewish (ASJ) AF: 0.999 AC: 21187 AN: 21206

East Asian (EAS) AF: 1.00 AC: 36175 AN: 36178

South Asian (SAS) AF: 0.999 AC: 70327 AN: 70364

European-Finnish (FIN) AF: 1.00 AC: 52987 AN: 52988

Middle Eastern (MID) AF: 0.988 AC: 4203 AN: 4256

European-Non Finnish (NFE) AF: 0.999 AC: 391360 AN: 391716

Other (OTH) AF: 0.987 AC: 34107 AN: 34570

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

African (AFR) AF: 0.858 AC: 35627 AN: 41504

American (AMR) AF: 0.982 AC: 15024 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.999 AC: 3467 AN: 3470

East Asian (EAS) AF: 1.00 AC: 5146 AN: 5146

South Asian (SAS) AF: 0.999 AC: 4817 AN: 4820

European-Finnish (FIN) AF: 1.00 AC: 10628 AN: 10628

Middle Eastern (MID) AF: 0.986 AC: 290 AN: 294

European-Non Finnish (NFE) AF: 0.999 AC: 67963 AN: 68038

Other (OTH) AF: 0.968 AC: 2049 AN: 2116

Alfa AF: 0.984 Hom.: 205117

Bravo AF: 0.953

Asia WGS AF: 0.976 AC: 3395 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.5
DANN	Benign	0.60
PhyloP100		0.046
Mutation Taster		=100/0	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: rs2412559; hg19: chr4-55151711; COSMIC: COSV99955340;