rs7677751

Variant names:

• chr4-54258293-C-T
• rs7677751
• NM_006206.6:c.-12-464C>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.-12-464C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 151,916 control chromosomes in the GnomAD database, including 2,979 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 0.18 (2979 hom., cov: 32)
• Consequence: PDGFRA NM_006206.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.28
• Publications: 26 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.268 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDGFRA	NM_006206.6	c.-12-464C>T		intron_variant	Intron 1 of 22	ENST00000257290.10	NP_006197.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDGFRA	ENST00000257290.10	c.-12-464C>T		intron_variant	Intron 1 of 22	1	NM_006206.6	ENSP00000257290.5
ENSG00000282278	ENST00000507166.5	c.1018-16632C>T		intron_variant	Intron 12 of 23	2		ENSP00000423325.1

Frequencies

GnomAD3 genomes AF: 0.184 AC: 27931 AN: 151798 Hom.: 2982 Cov.: 32

Gnomad AFR AF: 0.272

Gnomad AMI AF: 0.0888

Gnomad AMR AF: 0.235

Gnomad ASJ AF: 0.0648

Gnomad EAS AF: 0.193

Gnomad SAS AF: 0.246

Gnomad FIN AF: 0.147

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.128

Gnomad OTH AF: 0.167

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

GnomAD4 genome AF: 0.184 AC: 27946 AN: 151916 Hom.: 2979 Cov.: 32 AF XY: 0.186 AC XY: 13830 AN XY: 74222

African (AFR) AF: 0.272 AC: 11253 AN: 41396

American (AMR) AF: 0.235 AC: 3587 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.0648 AC: 225 AN: 3472

East Asian (EAS) AF: 0.193 AC: 992 AN: 5142

South Asian (SAS) AF: 0.246 AC: 1181 AN: 4806

European-Finnish (FIN) AF: 0.147 AC: 1548 AN: 10528

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.128 AC: 8704 AN: 67998

Other (OTH) AF: 0.164 AC: 345 AN: 2100

Alfa AF: 0.146 Hom.: 8226

Bravo AF: 0.195

Asia WGS AF: 0.245 AC: 851 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.021
DANN	Benign	0.22
PhyloP100		-1.3
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: rs7677751; hg19: chr4-55124460;