4-54229515-GAAA-GAAAAAA

Variant names:

• chr4-54229515-G-GAAA
• rs565335773
• NM_006206.6:c.-13+109_-13+111dupAAA

Variant summary

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

The NM_006206.6(PDGFRA):​c.-13+109_-13+111dupAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000443 in 180,450 control chromosomes in the GnomAD database, with no homozygous occurrence. There is a variant allele frequency bias in the population database for this variant (GnomAdExome4), 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: not found (cov: 21)
  • Exomes 𝑓: 0.000044 (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+109_-13+111dupAAA		intron	N/A	NP_006197.1	P16234-1
	PDGFRA	NM_001347828.2		c.-16+109_-16+111dupAAA		intron	N/A	NP_001334757.1
	PDGFRA	NM_001347827.2		c.-13+109_-13+111dupAAA		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+100_-13+101insAAA		intron	N/A	ENSP00000257290.5	P16234-1
	ENSG00000282278	ENST00000507166.5	TSL:2	c.1018-45410_1018-45409insAAA		intron	N/A	ENSP00000423325.1	A0A0B4J203
	PDGFRA	ENST00000508170.5	TSL:1	c.-13+100_-13+101insAAA		intron	N/A	ENSP00000425648.1	P16234-2

Frequencies

GnomAD3 genomes Cov.: 21

GnomAD4 exome AF: 0.0000443 AC: 8 AN: 180450 Hom.: 0 AF XY: 0.0000327 AC XY: 3 AN XY: 91628

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

African (AFR) AF: 0.000181 AC: 1 AN: 5514

American (AMR) AF: 0.000350 AC: 2 AN: 5708

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 6346

East Asian (EAS) AF: 0.000121 AC: 2 AN: 16522

South Asian (SAS) AF: 0.00 AC: 0 AN: 1672

European-Finnish (FIN) AF: 0.0000675 AC: 1 AN: 14820

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 892

European-Non Finnish (NFE) AF: 0.00000856 AC: 1 AN: 116796

Other (OTH) AF: 0.0000821 AC: 1 AN: 12180

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000000192603), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 21

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.5

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs565335773; hg19: chr4-55095682;