4-54286117-T-G

Position:

• chr4-54286117-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006206.6(PDGFRA):​c.2562+154T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.757 in 152,010 control chromosomes in the GnomAD database, including 45,146 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.76 (45146 hom., cov: 30)
• Consequence: PDGFRA NM_006206.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.42

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 4-54286117-T-G is Benign according to our data. Variant chr4-54286117-T-G is described in ClinVar as [Benign]. Clinvar id is 1246987.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.851 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDGFRA	NM_006206.6	c.2562+154T>G		intron_variant		ENST00000257290.10	NP_006197.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDGFRA	ENST00000257290.10	c.2562+154T>G		intron_variant		1	NM_006206.6	ENSP00000257290.5
ENSG00000282278	ENST00000507166.5	c.1842+154T>G		intron_variant		2		ENSP00000423325.1

Frequencies

GnomAD3 genomes AF: 0.757 AC: 114996 AN: 151892 Hom.: 45129 Cov.: 30

Gnomad AFR AF: 0.534

Gnomad AMI AF: 0.878

Gnomad AMR AF: 0.748

Gnomad ASJ AF: 0.931

Gnomad EAS AF: 0.857

Gnomad SAS AF: 0.764

Gnomad FIN AF: 0.870

Gnomad MID AF: 0.885

Gnomad NFE AF: 0.856

Gnomad OTH AF: 0.802

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.757 AC: 115053 AN: 152010 Hom.: 45146 Cov.: 30 AF XY: 0.759 AC XY: 56385 AN XY: 74314

Gnomad4 AFR AF: 0.534

Gnomad4 AMR AF: 0.748

Gnomad4 ASJ AF: 0.931

Gnomad4 EAS AF: 0.857

Gnomad4 SAS AF: 0.764

Gnomad4 FIN AF: 0.870

Gnomad4 NFE AF: 0.856

Gnomad4 OTH AF: 0.804

Alfa AF: 0.830 Hom.: 20748

Bravo AF: 0.738

Asia WGS AF: 0.777 AC: 2703 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 22, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.15
DANN	Benign	0.79

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

Publications

LitVar

Other links and lift over

dbSNP: rs4864872; hg19: chr4-55152284;