4-54229515-GAAA-GAA

Variant names:

• chr4-54229515-GA-G
• rs565335773
• NM_006206.6:c.-13+111delA

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_006206.6(PDGFRA):​c.-13+111delA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0374 in 305,086 control chromosomes in the GnomAD database, with no homozygous occurrence. There is a variant allele frequency bias in the population database for this variant (GnomAd4), which may indicate mosaicism or somatic mutations in the reference population data. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00035 (0 hom., cov: 21)
  • Exomes 𝑓: 0.070 (0 hom.)
• Consequence: PDGFRA NM_006206.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.51
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

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.-13+111delA		intron	N/A	NP_006197.1	P16234-1
	PDGFRA	NM_001347828.2		c.-16+111delA		intron	N/A	NP_001334757.1
	PDGFRA	NM_001347827.2		c.-13+111delA		intron	N/A	NP_001334756.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDGFRA	ENST00000257290.10	TSL:1 MANE Select	c.-13+101delA		intron	N/A	ENSP00000257290.5	P16234-1
	ENSG00000282278	ENST00000507166.5	TSL:2	c.1018-45409delA		intron	N/A	ENSP00000423325.1	A0A0B4J203
	PDGFRA	ENST00000508170.5	TSL:1	c.-13+101delA		intron	N/A	ENSP00000425648.1	P16234-2

Frequencies

GnomAD3 genomes AF: 0.000352 AC: 50 AN: 142164 Hom.: 0 Cov.: 21

Gnomad AFR AF: 0.000154

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000139

Gnomad ASJ AF: 0.000302

Gnomad EAS AF: 0.000204

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00147

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000432

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0698 AC: 11362 AN: 162876 Hom.: 0 AF XY: 0.0706 AC XY: 5823 AN XY: 82422

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0429 AC: 222 AN: 5170

American (AMR) AF: 0.0465 AC: 247 AN: 5316

Ashkenazi Jewish (ASJ) AF: 0.0955 AC: 533 AN: 5580

East Asian (EAS) AF: 0.0755 AC: 1114 AN: 14748

South Asian (SAS) AF: 0.0655 AC: 99 AN: 1512

European-Finnish (FIN) AF: 0.0698 AC: 939 AN: 13446

Middle Eastern (MID) AF: 0.0716 AC: 57 AN: 796

European-Non Finnish (NFE) AF: 0.0701 AC: 7376 AN: 105264

Other (OTH) AF: 0.0702 AC: 775 AN: 11044

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.000352 AC: 50 AN: 142210 Hom.: 0 Cov.: 21 AF XY: 0.000305 AC XY: 21 AN XY: 68874

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000154 AC: 6 AN: 39064

American (AMR) AF: 0.000139 AC: 2 AN: 14404

Ashkenazi Jewish (ASJ) AF: 0.000302 AC: 1 AN: 3312

East Asian (EAS) AF: 0.000205 AC: 1 AN: 4884

South Asian (SAS) AF: 0.00 AC: 0 AN: 4490

European-Finnish (FIN) AF: 0.00147 AC: 12 AN: 8148

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 274

European-Non Finnish (NFE) AF: 0.000432 AC: 28 AN: 64794

Other (OTH) AF: 0.00 AC: 0 AN: 1964

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000000000611067), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 67

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism

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: rs565335773; hg19: chr4-55095682; COSMIC: COSV57271818; COSMIC: COSV57271818;