8-17621984-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001372073.1(PDGFRL):c.505+782T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.53 in 151,972 control chromosomes in the GnomAD database, including 21,968 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.53 (21968 hom., cov: 32)
• Consequence: PDGFRL NM_001372073.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.250

Genes affected

PDGFRL (HGNC:8805): (platelet derived growth factor receptor like) This gene encodes a protein with significant sequence similarity to the ligand binding domain of platelet-derived growth factor receptor beta. Mutations in this gene, or deletion of a chromosomal segment containing this gene, are associated with sporadic hepatocellular carcinomas, colorectal cancers, and non-small cell lung cancers. This suggests this gene product may function as a tumor suppressor. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.626 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDGFRL	NM_001372073.1	c.505+782T>G		intron_variant		ENST00000251630.11
PDGFRL	NM_006207.2	c.505+782T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDGFRL	ENST00000251630.11	c.505+782T>G		intron_variant		5	NM_001372073.1	P1
PDGFRL	ENST00000541323.1	c.505+782T>G		intron_variant		2		P1

Frequencies

GnomAD3 genomes AF: 0.530 AC: 80524 AN: 151852 Hom.: 21974 Cov.: 32

Gnomad AFR AF: 0.378

Gnomad AMI AF: 0.579

Gnomad AMR AF: 0.544

Gnomad ASJ AF: 0.652

Gnomad EAS AF: 0.645

Gnomad SAS AF: 0.553

Gnomad FIN AF: 0.576

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.593

Gnomad OTH AF: 0.585

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

GnomAD4 genome AF: 0.530 AC: 80525 AN: 151972 Hom.: 21968 Cov.: 32 AF XY: 0.532 AC XY: 39478 AN XY: 74242

Gnomad4 AFR AF: 0.377

Gnomad4 AMR AF: 0.544

Gnomad4 ASJ AF: 0.652

Gnomad4 EAS AF: 0.645

Gnomad4 SAS AF: 0.552

Gnomad4 FIN AF: 0.576

Gnomad4 NFE AF: 0.593

Gnomad4 OTH AF: 0.577

Alfa AF: 0.544 Hom.: 3869

Bravo AF: 0.524

Asia WGS AF: 0.518 AC: 1802 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	3.0
Dann	Benign	0.38

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: rs2237834; hg19: chr8-17479493;