NM_006206.6:c.2440-50_2440-49insA

Variant names:

• chr4-54285791-T-TA
• rs3830355
• NM_006206.6:c.2440-50_2440-49insA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_006206.6(PDGFRA):​c.2440-50_2440-49insA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.831 in 1,600,954 control chromosomes in the GnomAD database, including 558,022 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.76 (45100 hom., cov: 0)
  • Exomes 𝑓: 0.84 (512922 hom.)
• Consequence: PDGFRA NM_006206.6 intron
• Clinical Significance: Benign criteria provided, single submitter U:1 B:1
• Conservation: PhyloP100: -1.30
• Publications: 11 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: Genomics England PanelApp, Ambry Genetics, G2P
• 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: Benign. The variant received -10 ACMG points.

• BP6: Variant 4-54285791-T-TA is Benign according to our data. Variant chr4-54285791-T-TA is described in ClinVar as Benign. ClinVar VariationId is 873180.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.85 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDGFRA	NM_006206.6	c.2440-50_2440-49insA		intron_variant	Intron 17 of 22	ENST00000257290.10	NP_006197.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDGFRA	ENST00000257290.10	c.2440-50_2440-49insA		intron_variant	Intron 17 of 22	1	NM_006206.6	ENSP00000257290.5
ENSG00000282278	ENST00000507166.5	c.1720-50_1720-49insA		intron_variant	Intron 18 of 23	2		ENSP00000423325.1

Frequencies

GnomAD3 genomes AF: 0.757 AC: 114952 AN: 151914 Hom.: 45087 Cov.: 0

Gnomad AFR AF: 0.535

Gnomad AMI AF: 0.878

Gnomad AMR AF: 0.747

Gnomad ASJ AF: 0.931

Gnomad EAS AF: 0.851

Gnomad SAS AF: 0.763

Gnomad FIN AF: 0.870

Gnomad MID AF: 0.886

Gnomad NFE AF: 0.856

Gnomad OTH AF: 0.801

GnomAD2 exomes AF: 0.805 AC: 201018 AN: 249854 AF XY: 0.814

Gnomad AFR exome AF: 0.525

Gnomad AMR exome AF: 0.677

Gnomad ASJ exome AF: 0.925

Gnomad EAS exome AF: 0.850

Gnomad FIN exome AF: 0.874

Gnomad NFE exome AF: 0.857

Gnomad OTH exome AF: 0.840

GnomAD4 exome AF: 0.839 AC: 1215338 AN: 1448922 Hom.: 512922 Cov.: 31 AF XY: 0.840 AC XY: 606287 AN XY: 721696

African (AFR) AF: 0.524 AC: 17448 AN: 33282

American (AMR) AF: 0.686 AC: 30676 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.921 AC: 23972 AN: 26036

East Asian (EAS) AF: 0.853 AC: 33801 AN: 39638

South Asian (SAS) AF: 0.785 AC: 67491 AN: 86004

European-Finnish (FIN) AF: 0.875 AC: 45567 AN: 52084

Middle Eastern (MID) AF: 0.887 AC: 4939 AN: 5570

European-Non Finnish (NFE) AF: 0.855 AC: 941374 AN: 1101658

Other (OTH) AF: 0.835 AC: 50070 AN: 59944

GnomAD4 genome AF: 0.756 AC: 115005 AN: 152032 Hom.: 45100 Cov.: 0 AF XY: 0.758 AC XY: 56361 AN XY: 74310

African (AFR) AF: 0.534 AC: 22142 AN: 41436

American (AMR) AF: 0.747 AC: 11423 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.931 AC: 3228 AN: 3468

East Asian (EAS) AF: 0.851 AC: 4387 AN: 5156

South Asian (SAS) AF: 0.763 AC: 3674 AN: 4814

European-Finnish (FIN) AF: 0.870 AC: 9215 AN: 10594

Middle Eastern (MID) AF: 0.891 AC: 262 AN: 294

European-Non Finnish (NFE) AF: 0.856 AC: 58185 AN: 67966

Other (OTH) AF: 0.802 AC: 1688 AN: 2106

Alfa AF: 0.828 Hom.: 8179

Bravo AF: 0.737

Asia WGS AF: 0.763 AC: 2653 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Uncertain:1 Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Squamous cell lung carcinoma Uncertain:1

May 05, 2020

Faculté Pluridciplinaire Nador, Université Mohamed Premier

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: clinical testing;in vivo

not provided Benign:1

Jun 22, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.3
Mutation Taster		=31/69	disease causing

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: rs3830355; hg19: chr4-55151958; COSMIC: COSV99955341;