NM_006206.6:c.-13+110_-13+111dupAA

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_006206.6(PDGFRA):​c.-13+110_-13+111dupAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00666 in 321,666 control chromosomes in the GnomAD database, including 9 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0061 (9 hom., cov: 21)
  • Exomes 𝑓: 0.0071 (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

Verdict is Benign. Variant got -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.00714 (1281/179320) while in subpopulation AFR AF= 0.024 (131/5464). AF 95% confidence interval is 0.0206. There are 0 homozygotes in gnomad4_exome. There are 627 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 862 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDGFRA	NM_006206.6	c.-13+110_-13+111dupAA		intron_variant	Intron 1 of 22	ENST00000257290.10	NP_006197.1
PDGFRA	NM_001347828.2	c.-16+110_-16+111dupAA		intron_variant	Intron 1 of 23		NP_001334757.1
PDGFRA	NM_001347827.2	c.-13+110_-13+111dupAA		intron_variant	Intron 1 of 16		NP_001334756.1
PDGFRA	XM_006714041.4	c.-16+110_-16+111dupAA		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+100_-13+101insAA		intron_variant	Intron 1 of 22	1	NM_006206.6	ENSP00000257290.5
ENSG00000282278	ENST00000507166.5	c.1018-45410_1018-45409insAA		intron_variant	Intron 12 of 23	2		ENSP00000423325.1

Frequencies

GnomAD3 genomes AF: 0.00604 AC: 860 AN: 142300 Hom.: 9 Cov.: 21

Gnomad AFR AF: 0.0145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00507

Gnomad ASJ AF: 0.00151

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000443

Gnomad FIN AF: 0.00183

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00291

Gnomad OTH AF: 0.00512

GnomAD4 exome AF: 0.00714 AC: 1281 AN: 179320 Hom.: 0 AF XY: 0.00688 AC XY: 627 AN XY: 91068

Gnomad4 AFR exome AF: 0.0240

Gnomad4 AMR exome AF: 0.0127

Gnomad4 ASJ exome AF: 0.00332

Gnomad4 EAS exome AF: 0.00310

Gnomad4 SAS exome AF: 0.00481

Gnomad4 FIN exome AF: 0.00489

Gnomad4 NFE exome AF: 0.00700

Gnomad4 OTH exome AF: 0.00891

GnomAD4 genome AF: 0.00606 AC: 862 AN: 142346 Hom.: 9 Cov.: 21 AF XY: 0.00625 AC XY: 431 AN XY: 68944

Gnomad4 AFR AF: 0.0146

Gnomad4 AMR AF: 0.00507

Gnomad4 ASJ AF: 0.00151

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000445

Gnomad4 FIN AF: 0.00183

Gnomad4 NFE AF: 0.00290

Gnomad4 OTH AF: 0.00509

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs565335773; hg19: chr4-55095682;