4-54258424-A-G

Variant names:

• chr4-54258424-A-G
• rs9991165
• NM_006206.6:c.-12-333A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_006206.6(PDGFRA):​c.-12-333A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.23 in 152,010 control chromosomes in the GnomAD database, including 4,905 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.23 (4905 hom., cov: 32)
• Consequence: PDGFRA NM_006206.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.47
• Publications: 4 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP6: Variant 4-54258424-A-G is Benign according to our data. Variant chr4-54258424-A-G is described in ClinVar as Benign. ClinVar VariationId is 1263122.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.366 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.-12-333A>G		intron	N/A	NP_006197.1	P16234-1
	PDGFRA	NM_001347828.2		c.64-333A>G		intron	N/A	NP_001334757.1
	PDGFRA	NM_001347830.2		c.28-333A>G		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.-12-333A>G		intron	N/A	ENSP00000257290.5	P16234-1
	ENSG00000282278	ENST00000507166.5	TSL:2	c.1018-16501A>G		intron	N/A	ENSP00000423325.1	A0A0B4J203
	PDGFRA	ENST00000508170.5	TSL:1	c.-12-333A>G		intron	N/A	ENSP00000425648.1	P16234-2

Frequencies

GnomAD3 genomes AF: 0.230 AC: 34878 AN: 151892 Hom.: 4895 Cov.: 32

Gnomad AFR AF: 0.371

Gnomad AMI AF: 0.0921

Gnomad AMR AF: 0.321

Gnomad ASJ AF: 0.0738

Gnomad EAS AF: 0.184

Gnomad SAS AF: 0.251

Gnomad FIN AF: 0.153

Gnomad MID AF: 0.0987

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.201

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

GnomAD4 genome AF: 0.230 AC: 34933 AN: 152010 Hom.: 4905 Cov.: 32 AF XY: 0.231 AC XY: 17160 AN XY: 74322

African (AFR) AF: 0.371 AC: 15372 AN: 41414

American (AMR) AF: 0.321 AC: 4905 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.0738 AC: 256 AN: 3470

East Asian (EAS) AF: 0.184 AC: 951 AN: 5166

South Asian (SAS) AF: 0.251 AC: 1208 AN: 4820

European-Finnish (FIN) AF: 0.153 AC: 1620 AN: 10568

Middle Eastern (MID) AF: 0.106 AC: 31 AN: 292

European-Non Finnish (NFE) AF: 0.148 AC: 10088 AN: 67998

Other (OTH) AF: 0.199 AC: 418 AN: 2104

Alfa AF: 0.188 Hom.: 411

Bravo AF: 0.248

Asia WGS AF: 0.259 AC: 901 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	9.0
DANN	Benign	0.91
PhyloP100		1.5
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: rs9991165; hg19: chr4-55124591;