4-54229515-GAAA-GAAAAAAA

Variant names:

• chr4-54229515-G-GAAAA
• rs565335773
• NM_006206.6:c.-13+108_-13+111dupAAAA

Variant summary

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

The NM_006206.6(PDGFRA):​c.-13+108_-13+111dupAAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000554 in 180,492 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: not found (cov: 21)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: PDGFRA NM_006206.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.51

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]

ENSG00000282278 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDGFRA	NM_006206.6	c.-13+108_-13+111dupAAAA		intron_variant	Intron 1 of 22	ENST00000257290.10	NP_006197.1
PDGFRA	NM_001347828.2	c.-16+108_-16+111dupAAAA		intron_variant	Intron 1 of 23		NP_001334757.1
PDGFRA	NM_001347827.2	c.-13+108_-13+111dupAAAA		intron_variant	Intron 1 of 16		NP_001334756.1
PDGFRA	XM_006714041.4	c.-16+108_-16+111dupAAAA		intron_variant	Intron 1 of 17		XP_006714104.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDGFRA	ENST00000257290.10	c.-13+108_-13+111dupAAAA		intron_variant	Intron 1 of 22	1	NM_006206.6	ENSP00000257290.5
ENSG00000282278	ENST00000507166.5	c.1018-45402_1018-45399dupAAAA		intron_variant	Intron 12 of 23	2		ENSP00000423325.1

Frequencies

GnomAD3 genomes Cov.: 21

GnomAD4 exome AF: 0.00000554 AC: 1 AN: 180492 Hom.: 0 AF XY: 0.0000109 AC XY: 1 AN XY: 91640

⚠️ 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: 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: 16526

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 14826

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 116820

Other (OTH) AF: 0.00 AC: 0 AN: 12182

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 21

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.5

Splicing

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

Publications

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Other links and lift over

dbSNP: rs565335773; hg19: chr4-55095682;