4-54286117-T-G

Variant names:

• chr4-54286117-T-G
• rs4864872
• NM_006206.6:c.2562+154T>G

Variant summary

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

The NM_001347828.2(PDGFRA):​c.2637+154T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.757 in 152,010 control chromosomes in the GnomAD database, including 45,146 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.76 (45146 hom., cov: 30)
• Consequence: PDGFRA NM_001347828.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.42
• Publications: 8 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=-0.89).
• BP6: Variant 4-54286117-T-G is Benign according to our data. Variant chr4-54286117-T-G is described in ClinVar as Benign. ClinVar VariationId is 1246987.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.851 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001347828.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDGFRA	NM_006206.6	MANE Select	c.2562+154T>G		intron	N/A	NP_006197.1
	PDGFRA	NM_001347828.2		c.2637+154T>G		intron	N/A	NP_001334757.1
	PDGFRA	NM_001347830.2		c.2601+154T>G		intron	N/A	NP_001334759.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDGFRA	ENST00000257290.10	TSL:1 MANE Select	c.2562+154T>G		intron	N/A	ENSP00000257290.5
	ENSG00000282278	ENST00000507166.5	TSL:2	c.1842+154T>G		intron	N/A	ENSP00000423325.1
	PDGFRA	ENST00000870889.1		c.2562+154T>G		intron	N/A	ENSP00000540948.1

Frequencies

GnomAD3 genomes AF: 0.757 AC: 114996 AN: 151892 Hom.: 45129 Cov.: 30

Gnomad AFR AF: 0.534

Gnomad AMI AF: 0.878

Gnomad AMR AF: 0.748

Gnomad ASJ AF: 0.931

Gnomad EAS AF: 0.857

Gnomad SAS AF: 0.764

Gnomad FIN AF: 0.870

Gnomad MID AF: 0.885

Gnomad NFE AF: 0.856

Gnomad OTH AF: 0.802

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

GnomAD4 genome AF: 0.757 AC: 115053 AN: 152010 Hom.: 45146 Cov.: 30 AF XY: 0.759 AC XY: 56385 AN XY: 74314

African (AFR) AF: 0.534 AC: 22128 AN: 41426

American (AMR) AF: 0.748 AC: 11418 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.931 AC: 3232 AN: 3472

East Asian (EAS) AF: 0.857 AC: 4403 AN: 5140

South Asian (SAS) AF: 0.764 AC: 3686 AN: 4822

European-Finnish (FIN) AF: 0.870 AC: 9204 AN: 10584

Middle Eastern (MID) AF: 0.890 AC: 260 AN: 292

European-Non Finnish (NFE) AF: 0.856 AC: 58224 AN: 67992

Other (OTH) AF: 0.804 AC: 1697 AN: 2110

Alfa AF: 0.831 Hom.: 23516

Bravo AF: 0.738

Asia WGS AF: 0.777 AC: 2703 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.15
DANN	Benign	0.79
PhyloP100		-2.4
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: rs4864872; hg19: chr4-55152284;