chr4-54229515-GAA-G

Variant names:

• chr4-54229515-GAA-G
• rs565335773
• NM_006206.6:c.-13+110_-13+111delAA

Variant summary

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

The NM_006206.6(PDGFRA):​c.-13+110_-13+111delAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000479 in 319,746 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: 𝑓 0.000014 (0 hom., cov: 21)
  • Exomes 𝑓: 0.00085 (0 hom.)
• Consequence: PDGFRA NM_006206.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.184
• 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: Labcorp Genetics (formerly Invitae), ClinGen
• polyps, multiple and recurrent inflammatory fibroid, gastrointestinal

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, G2P, 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+110_-13+111delAA		intron	N/A	NP_006197.1	P16234-1
	PDGFRA	NM_001347828.2		c.-16+110_-16+111delAA		intron	N/A	NP_001334757.1
	PDGFRA	NM_001347827.2		c.-13+110_-13+111delAA		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+101_-13+102delAA		intron	N/A	ENSP00000257290.5	P16234-1
	ENSG00000282278	ENST00000507166.5	TSL:2	c.1018-45409_1018-45408delAA		intron	N/A	ENSP00000423325.1	A0A0B4J203
	PDGFRA	ENST00000508170.5	TSL:1	c.-13+101_-13+102delAA		intron	N/A	ENSP00000425648.1	P16234-2

Frequencies

GnomAD3 genomes AF: 0.0000141 AC: 2 AN: 142296 Hom.: 0 Cov.: 21

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000244

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000851 AC: 151 AN: 177406 Hom.: 0 AF XY: 0.000822 AC XY: 74 AN XY: 90058

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

African (AFR) AF: 0.000736 AC: 4 AN: 5436

American (AMR) AF: 0.000531 AC: 3 AN: 5652

Ashkenazi Jewish (ASJ) AF: 0.00129 AC: 8 AN: 6190

East Asian (EAS) AF: 0.00117 AC: 19 AN: 16198

South Asian (SAS) AF: 0.00 AC: 0 AN: 1650

European-Finnish (FIN) AF: 0.00110 AC: 16 AN: 14570

Middle Eastern (MID) AF: 0.00113 AC: 1 AN: 882

European-Non Finnish (NFE) AF: 0.000731 AC: 84 AN: 114860

Other (OTH) AF: 0.00134 AC: 16 AN: 11968

⚠️ 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: 0.0000141 AC: 2 AN: 142340 Hom.: 0 Cov.: 21 AF XY: 0.00 AC XY: 0 AN XY: 68928

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

African (AFR) AF: 0.00 AC: 0 AN: 39072

American (AMR) AF: 0.00 AC: 0 AN: 14410

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3320

East Asian (EAS) AF: 0.00 AC: 0 AN: 4884

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

European-Finnish (FIN) AF: 0.000244 AC: 2 AN: 8184

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 64864

Other (OTH) AF: 0.00 AC: 0 AN: 1966

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.18

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;