rs565335773

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr4-54229515-GAAA-G
• chr4-54229515-GAAA-GA
• chr4-54229515-GAAA-GAA
• chr4-54229515-GAAA-GAAAA
• chr4-54229515-GAAA-GAAAAA
• chr4-54229515-GAAA-GAAAAAA
• chr4-54229515-GAAA-GAAAAAAA
• chr4-54229515-GAAA-GAAAAAAAAAAAA

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_006206.6(PDGFRA):​c.-13+109_-13+111delAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000166 in 180,422 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 21)
  • Exomes 𝑓: 0.000017 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PDGFRA NM_006206.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0530
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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+111delAAA		intron	N/A	NP_006197.1	P16234-1
	PDGFRA	NM_001347828.2		c.-16+109_-16+111delAAA		intron	N/A	NP_001334757.1
	PDGFRA	NM_001347827.2		c.-13+109_-13+111delAAA		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+103delAAA		intron	N/A	ENSP00000257290.5	P16234-1
	ENSG00000282278	ENST00000507166.5	TSL:2	c.1018-45409_1018-45407delAAA		intron	N/A	ENSP00000423325.1	A0A0B4J203
	PDGFRA	ENST00000508170.5	TSL:1	c.-13+101_-13+103delAAA		intron	N/A	ENSP00000425648.1	P16234-2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 142310 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: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000166 AC: 3 AN: 180422 Hom.: 0 AF XY: 0.0000218 AC XY: 2 AN XY: 91610

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

African (AFR) AF: 0.00 AC: 0 AN: 5516

American (AMR) AF: 0.00 AC: 0 AN: 5712

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 16524

South Asian (SAS) AF: 0.00 AC: 0 AN: 1670

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 14818

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

European-Non Finnish (NFE) AF: 0.0000171 AC: 2 AN: 116764

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

⚠️ 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 Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 142310 Hom.: 0 Cov.: 21 AF XY: 0.00 AC XY: 0 AN XY: 68886

African (AFR) AF: 0.00 AC: 0 AN: 38986

American (AMR) AF: 0.00 AC: 0 AN: 14396

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 4900

South Asian (SAS) AF: 0.00 AC: 0 AN: 4510

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8186

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 298

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 64884

Other (OTH) AF: 0.00 AC: 0 AN: 1954

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.053

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;