rs7660759

Variant names:

• chr4-54268315-G-T
• rs7660759
• NM_006206.6:c.1121+574G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006206.6(PDGFRA):​c.1121+574G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0321 in 152,204 control chromosomes in the GnomAD database, including 269 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.032 (269 hom., cov: 32)
• Consequence: PDGFRA NM_006206.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0790
• Publications: 0 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: G2P, Ambry Genetics, Genomics England PanelApp
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.109 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDGFRA	NM_006206.6	MANE Select	c.1121+574G>T		intron	N/A	NP_006197.1	P16234-1
	PDGFRA	NM_001347828.2		c.1196+574G>T		intron	N/A	NP_001334757.1
	PDGFRA	NM_001347830.2		c.1160+574G>T		intron	N/A	NP_001334759.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDGFRA	ENST00000257290.10	TSL:1 MANE Select	c.1121+574G>T		intron	N/A	ENSP00000257290.5	P16234-1
	ENSG00000282278	ENST00000507166.5	TSL:2	c.1018-6610G>T		intron	N/A	ENSP00000423325.1	A0A0B4J203
	PDGFRA	ENST00000509092.5	TSL:1	n.939+574G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0320 AC: 4869 AN: 152086 Hom.: 269 Cov.: 32

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0100

Gnomad ASJ AF: 0.00375

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000829

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000323

Gnomad OTH AF: 0.0220

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

GnomAD4 genome AF: 0.0321 AC: 4887 AN: 152204 Hom.: 269 Cov.: 32 AF XY: 0.0306 AC XY: 2276 AN XY: 74424

African (AFR) AF: 0.112 AC: 4650 AN: 41500

American (AMR) AF: 0.00994 AC: 152 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00375 AC: 13 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000323 AC: 22 AN: 68014

Other (OTH) AF: 0.0218 AC: 46 AN: 2112

Alfa AF: 0.0277 Hom.: 21

Bravo AF: 0.0361

Asia WGS AF: 0.0110 AC: 39 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.7
DANN	Benign	0.40
PhyloP100		0.079
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: rs7660759; hg19: chr4-55134482;