4-54277410-G-A

Variant names:

• chr4-54277410-G-A
• rs10028020
• NM_006206.6:c.1809G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_006206.6(PDGFRA):​c.1809G>A​(p.Ala603Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 1,612,388 control chromosomes in the GnomAD database, including 16,013 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.17 (3008 hom., cov: 31)
  • Exomes 𝑓: 0.12 (13005 hom.)
• Consequence: PDGFRA NM_006206.6 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -5.22
• Publications: 25 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 4-54277410-G-A is Benign according to our data. Variant chr4-54277410-G-A is described in ClinVar as Benign. ClinVar VariationId is 259950.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-5.22 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.301 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.1809G>A	p.Ala603Ala	synonymous	Exon 13 of 23	NP_006197.1	P16234-1
	PDGFRA	NM_001347828.2		c.1884G>A	p.Ala628Ala	synonymous	Exon 14 of 24	NP_001334757.1
	PDGFRA	NM_001347830.2		c.1848G>A	p.Ala616Ala	synonymous	Exon 13 of 23	NP_001334759.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDGFRA	ENST00000257290.10	TSL:1 MANE Select	c.1809G>A	p.Ala603Ala	synonymous	Exon 13 of 23	ENSP00000257290.5	P16234-1
	ENSG00000282278	ENST00000507166.5	TSL:2	c.1089G>A	p.Ala363Ala	synonymous	Exon 14 of 24	ENSP00000423325.1	A0A0B4J203
	PDGFRA	ENST00000507536.1	TSL:1	n.235G>A		non_coding_transcript_exon	Exon 1 of 5

Frequencies

GnomAD3 genomes AF: 0.175 AC: 26546 AN: 151862 Hom.: 3009 Cov.: 31

Gnomad AFR AF: 0.306

Gnomad AMI AF: 0.0998

Gnomad AMR AF: 0.215

Gnomad ASJ AF: 0.0545

Gnomad EAS AF: 0.145

Gnomad SAS AF: 0.231

Gnomad FIN AF: 0.117

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.145

GnomAD2 exomes AF: 0.159 AC: 40099 AN: 251462 AF XY: 0.153

Gnomad AFR exome AF: 0.312

Gnomad AMR exome AF: 0.302

Gnomad ASJ exome AF: 0.0583

Gnomad EAS exome AF: 0.145

Gnomad FIN exome AF: 0.113

Gnomad NFE exome AF: 0.102

Gnomad OTH exome AF: 0.125

GnomAD4 exome AF: 0.121 AC: 176694 AN: 1460408 Hom.: 13005 Cov.: 31 AF XY: 0.121 AC XY: 88234 AN XY: 726574

African (AFR) AF: 0.308 AC: 10289 AN: 33428

American (AMR) AF: 0.290 AC: 12985 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.0633 AC: 1653 AN: 26132

East Asian (EAS) AF: 0.144 AC: 5718 AN: 39686

South Asian (SAS) AF: 0.208 AC: 17971 AN: 86212

European-Finnish (FIN) AF: 0.109 AC: 5847 AN: 53418

Middle Eastern (MID) AF: 0.0827 AC: 477 AN: 5766

European-Non Finnish (NFE) AF: 0.103 AC: 114429 AN: 1110716

Other (OTH) AF: 0.121 AC: 7325 AN: 60332

GnomAD4 genome AF: 0.175 AC: 26560 AN: 151980 Hom.: 3008 Cov.: 31 AF XY: 0.177 AC XY: 13117 AN XY: 74274

African (AFR) AF: 0.305 AC: 12643 AN: 41392

American (AMR) AF: 0.215 AC: 3283 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0545 AC: 189 AN: 3468

East Asian (EAS) AF: 0.145 AC: 744 AN: 5134

South Asian (SAS) AF: 0.232 AC: 1114 AN: 4810

European-Finnish (FIN) AF: 0.117 AC: 1240 AN: 10584

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.102 AC: 6929 AN: 67990

Other (OTH) AF: 0.143 AC: 302 AN: 2114

Alfa AF: 0.131 Hom.: 971

Bravo AF: 0.187

Asia WGS AF: 0.200 AC: 696 AN: 3478

EpiCase AF: 0.0973

EpiControl AF: 0.0957

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Gastrointestinal stromal tumor (2)
-	-	2	not provided (2)
-	-	1	Hereditary cancer-predisposing syndrome (1)
-	-	1	Idiopathic hypereosinophilic syndrome (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.1
DANN	Benign	0.76
PhyloP100		-5.2
Mutation Taster		=97/3	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: rs10028020; hg19: chr4-55143577; COSMIC: COSV57265177;