Variant 8-17577291-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001372073.1(PDGFRL):c.39C>G(p.His13Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000868 in 1,612,832 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 30)

Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

PDGFRL
NM_001372073.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.144

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13594738).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDGFRL	NM_001372073.1 linkuse as main transcript	c.39C>G	p.His13Gln	missense_variant	1/6	ENST00000251630.11
PDGFRL	NM_006207.2 linkuse as main transcript	c.39C>G	p.His13Gln	missense_variant	2/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
PDGFRL	ENST00000251630.11 linkuse as main transcript	c.39C>G	p.His13Gln	missense_variant	1/6	5	NM_001372073.1	P1
PDGFRL	ENST00000541323.1 linkuse as main transcript	c.39C>G	p.His13Gln	missense_variant	2/7	2		P1
PDGFRL	ENST00000673645.1 linkuse as main transcript	c.39C>G	p.His13Gln	missense_variant	2/4

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151924

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000806

AC:

AN:

247992

Hom.:

AF XY:

0.00

AC XY:

AN XY:

134326

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000179

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000821

AC:

AN:

1460908

Hom.:

Cov.:

AF XY:

0.00000826

AC XY:

AN XY:

726696

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000900

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000132

AC:

AN:

151924

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74190

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

EpiCase

AF:

0.00

EpiControl

AF:

0.0000594

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

Sep 01, 2021

The c.39C>G (p.H13Q) alteration is located in exon 2 (coding exon 1) of the PDGFRL gene. This alteration results from a C to G substitution at nucleotide position 39, causing the histidine (H) at amino acid position 13 to be replaced by a glutamine (Q). 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

0.093

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.53

Cadd

Benign

Dann

Benign

0.60

DEOGEN2

Benign

0.016

T;T

Eigen

Benign

-0.71

Eigen_PC

Benign

-0.72

FATHMM_MKL

Benign

0.47

M_CAP

Benign

0.0074

MetaRNN

Benign

0.14

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

L;L

MutationTaster

Benign

0.93

N;N;N

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-0.47

N;N

REVEL

Benign

0.044

Sift

Benign

0.30

T;T

Sift4G

Benign

0.31

T;T

Polyphen

0.0030

B;B

Vest4

0.40

MutPred

0.51

Gain of sheet (P = 0.0221);Gain of sheet (P = 0.0221);

MVP

0.25

MPC

0.0057

ClinPred

0.098

GERP RS

0.79

Varity_R

0.097

gMVP

0.31

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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