Variant 8-17621101-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001372073.1(PDGFRL):c.404C>T(p.Ser135Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000602 in 1,612,000 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00028 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000037 ( 0 hom. )

Consequence

PDGFRL
NM_001372073.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.41

Variant links:

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]

PDGFRL links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.045567244).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDGFRL	NM_001372073.1 linkuse as main transcript	c.404C>T	p.Ser135Leu	missense_variant	3/6	ENST00000251630.11	NP_001359002.1
PDGFRL	NM_006207.2 linkuse as main transcript	c.404C>T	p.Ser135Leu	missense_variant	4/7		NP_006198.1	Q15198

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PDGFRL	ENST00000251630.11 linkuse as main transcript	c.404C>T	p.Ser135Leu	missense_variant	3/6	5	NM_001372073.1	ENSP00000251630.4	Q15198
PDGFRL	ENST00000541323.1 linkuse as main transcript	c.404C>T	p.Ser135Leu	missense_variant	4/7	2		ENSP00000444211.1	Q15198
PDGFRL	ENST00000673645.1 linkuse as main transcript	c.*18C>T		downstream_gene_variant				ENSP00000501219.1	A0A669KBD1

Frequencies

GnomAD3 genomes

AF:

0.000250

AC:

AN:

152004

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000772

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000389

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000918

AC:

AN:

250466

Hom.:

AF XY:

0.000103

AC XY:

AN XY:

135406

show subpopulations

Gnomad AFR exome

AF:

0.00117

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000545

Gnomad SAS exome

AF:

0.0000328

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000370

AC:

AN:

1459878

Hom.:

Cov.:

AF XY:

0.0000358

AC XY:

AN XY:

726214

show subpopulations

Gnomad4 AFR exome

AF:

0.000688

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0000349

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000207

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.000283

AC:

AN:

152122

Hom.:

Cov.:

AF XY:

0.000350

AC XY:

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.000891

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000390

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000803

Hom.:

Bravo

AF:

0.000355

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000107

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 27, 2024

The c.404C>T (p.S135L) alteration is located in exon 4 (coding exon 3) of the PDGFRL gene. This alteration results from a C to T substitution at nucleotide position 404, causing the serine (S) at amino acid position 135 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.040

T;T

Eigen

Benign

-0.16

Eigen_PC

Benign

-0.056

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.93

.;D

M_CAP

Benign

0.0098

MetaRNN

Benign

0.046

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.90

L;L

PrimateAI

Benign

0.43

PROVEAN

Benign

-1.6

N;N

REVEL

Benign

0.17

Sift

Benign

0.17

T;T

Sift4G

Uncertain

0.0070

D;D

Polyphen

0.29

B;B

Vest4

0.29

MVP

0.42

MPC

0.0063

ClinPred

0.063

GERP RS

5.3

Varity_R

0.14

gMVP

0.49

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over