NM_006206.6:c.2613C>T

Variant names:

• chr4-54287480-C-T
• rs774190208
• NM_006206.6:c.2613C>T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

The NM_006206.6(PDGFRA):​c.2613C>T​(p.Leu871Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000119 in 1,428,296 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. L871L) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: PDGFRA NM_006206.6 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.87
• Publications: 1 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: Benign. The variant received -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).
• BP6: Variant 4-54287480-C-T is Benign according to our data. Variant chr4-54287480-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 414494.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.87 with no splicing effect.
• BS2: High AC in GnomAdExome4 at 17 Unknown,AD gene.

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.2613C>T	p.Leu871Leu	synonymous	Exon 19 of 23	NP_006197.1	P16234-1
	PDGFRA	NM_001347828.2		c.2688C>T	p.Leu896Leu	synonymous	Exon 20 of 24	NP_001334757.1
	PDGFRA	NM_001347830.2		c.2652C>T	p.Leu884Leu	synonymous	Exon 19 of 23	NP_001334759.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDGFRA	ENST00000257290.10	TSL:1 MANE Select	c.2613C>T	p.Leu871Leu	synonymous	Exon 19 of 23	ENSP00000257290.5	P16234-1
	ENSG00000282278	ENST00000507166.5	TSL:2	c.1893C>T	p.Leu631Leu	synonymous	Exon 20 of 24	ENSP00000423325.1	A0A0B4J203
	PDGFRA	ENST00000870889.1		c.2613C>T	p.Leu871Leu	synonymous	Exon 19 of 23	ENSP00000540948.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000359 AC: 9 AN: 251016 AF XY: 0.0000442

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000706

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000119 AC: 17 AN: 1428296 Hom.: 0 Cov.: 25 AF XY: 0.0000168 AC XY: 12 AN XY: 712940

African (AFR) AF: 0.00 AC: 0 AN: 32786

American (AMR) AF: 0.00 AC: 0 AN: 44676

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25928

East Asian (EAS) AF: 0.00 AC: 0 AN: 39530

South Asian (SAS) AF: 0.00 AC: 0 AN: 85518

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53402

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5714

European-Non Finnish (NFE) AF: 0.0000157 AC: 17 AN: 1081526

Other (OTH) AF: 0.00 AC: 0 AN: 59216

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000868 Hom.: 0

Bravo AF: 0.0000113

EpiCase AF: 0.00

EpiControl AF: 0.000178

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Gastrointestinal stromal tumor (1)
-	-	1	Hereditary cancer-predisposing syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
CADD	Benign	8.1
DANN	Benign	0.75
PhyloP100		1.9
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs774190208; hg19: chr4-55153647;