rs2307049

Variant names:

• chr4-54263987-G-A
• rs2307049
• ENST00000508170.5:c.*31G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000508170.5(PDGFRA):​c.*31G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 1,502,626 control chromosomes in the GnomAD database, including 19,525 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.18 (2992 hom., cov: 31)
  • Exomes 𝑓: 0.14 (16533 hom.)
• Consequence: PDGFRA ENST00000508170.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.314
• Publications: 11 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=-0.92).
• BP6: Variant 4-54263987-G-A is Benign according to our data. Variant chr4-54263987-G-A is described in ClinVar as Benign. ClinVar VariationId is 1276038.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.283 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDGFRA	NM_006206.6	c.628+60G>A		intron_variant	Intron 4 of 22	ENST00000257290.10	NP_006197.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDGFRA	ENST00000257290.10	c.628+60G>A		intron_variant	Intron 4 of 22	1	NM_006206.6	ENSP00000257290.5
ENSG00000282278	ENST00000507166.5	c.1018-10938G>A		intron_variant	Intron 12 of 23	2		ENSP00000423325.1

Frequencies

GnomAD3 genomes AF: 0.181 AC: 27392 AN: 151540 Hom.: 2992 Cov.: 31

Gnomad AFR AF: 0.254

Gnomad AMI AF: 0.0899

Gnomad AMR AF: 0.290

Gnomad ASJ AF: 0.0703

Gnomad EAS AF: 0.183

Gnomad SAS AF: 0.246

Gnomad FIN AF: 0.126

Gnomad MID AF: 0.0510

Gnomad NFE AF: 0.123

Gnomad OTH AF: 0.155

GnomAD2 exomes AF: 0.220 AC: 42546 AN: 193732 AF XY: 0.207

Gnomad AFR exome AF: 0.282

Gnomad AMR exome AF: 0.453

Gnomad ASJ exome AF: 0.0834

Gnomad EAS exome AF: 0.209

Gnomad FIN exome AF: 0.149

Gnomad NFE exome AF: 0.143

Gnomad OTH exome AF: 0.176

GnomAD4 exome AF: 0.143 AC: 193429 AN: 1350972 Hom.: 16533 Cov.: 21 AF XY: 0.143 AC XY: 96731 AN XY: 675648

African (AFR) AF: 0.255 AC: 7758 AN: 30382

American (AMR) AF: 0.418 AC: 17095 AN: 40908

Ashkenazi Jewish (ASJ) AF: 0.0776 AC: 1929 AN: 24856

East Asian (EAS) AF: 0.167 AC: 6487 AN: 38846

South Asian (SAS) AF: 0.228 AC: 18098 AN: 79308

European-Finnish (FIN) AF: 0.121 AC: 5082 AN: 41892

Middle Eastern (MID) AF: 0.100 AC: 543 AN: 5418

European-Non Finnish (NFE) AF: 0.124 AC: 128174 AN: 1032766

Other (OTH) AF: 0.146 AC: 8263 AN: 56596

GnomAD4 genome AF: 0.181 AC: 27423 AN: 151654 Hom.: 2992 Cov.: 31 AF XY: 0.184 AC XY: 13600 AN XY: 74058

African (AFR) AF: 0.254 AC: 10504 AN: 41320

American (AMR) AF: 0.290 AC: 4422 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.0703 AC: 244 AN: 3472

East Asian (EAS) AF: 0.184 AC: 947 AN: 5158

South Asian (SAS) AF: 0.247 AC: 1181 AN: 4790

European-Finnish (FIN) AF: 0.126 AC: 1319 AN: 10456

Middle Eastern (MID) AF: 0.0548 AC: 16 AN: 292

European-Non Finnish (NFE) AF: 0.123 AC: 8384 AN: 67896

Other (OTH) AF: 0.154 AC: 324 AN: 2106

Alfa AF: 0.138 Hom.: 2458

Bravo AF: 0.195

Asia WGS AF: 0.244 AC: 844 AN: 3466

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Aug 10, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.3
DANN	Benign	0.58
PhyloP100		-0.31
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: rs2307049; hg19: chr4-55130154;