Variant chr8-17577264-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001372073.1(PDGFRL):c.12G>T(p.Trp4Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000384 in 1,612,926 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0020 ( 2 hom., cov: 30)

Exomes 𝑓: 0.00022 ( 1 hom. )

Consequence

PDGFRL
NM_001372073.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.79

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 Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.010438532).

BP6

Variant 8-17577264-G-T is Benign according to our data. Variant chr8-17577264-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 730123.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDGFRL	NM_001372073.1 linkuse as main transcript	c.12G>T	p.Trp4Cys	missense_variant	1/6	ENST00000251630.11	NP_001359002.1
PDGFRL	NM_006207.2 linkuse as main transcript	c.12G>T	p.Trp4Cys	missense_variant	2/7		NP_006198.1	Q15198

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PDGFRL	ENST00000251630.11 linkuse as main transcript	c.12G>T	p.Trp4Cys	missense_variant	1/6	5	NM_001372073.1	ENSP00000251630.4	Q15198
PDGFRL	ENST00000541323.1 linkuse as main transcript	c.12G>T	p.Trp4Cys	missense_variant	2/7	2		ENSP00000444211.1	Q15198
PDGFRL	ENST00000673645.1 linkuse as main transcript	c.12G>T	p.Trp4Cys	missense_variant	2/4			ENSP00000501219.1	A0A669KBD1

Frequencies

GnomAD3 genomes

AF:

0.00196

AC:

298

AN:

151872

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00690

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.0000883

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.000518

AC:

128

AN:

247306

Hom.:

AF XY:

0.000358

AC XY:

AN XY:

134028

show subpopulations

Gnomad AFR exome

AF:

0.00734

Gnomad AMR exome

AF:

0.000262

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:

0.00000900

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.000218

AC:

319

AN:

1460936

Hom.:

Cov.:

AF XY:

0.000187

AC XY:

136

AN XY:

726702

show subpopulations

Gnomad4 AFR exome

AF:

0.00810

Gnomad4 AMR exome

AF:

0.000291

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000233

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.000497

GnomAD4 genome

AF:

0.00197

AC:

300

AN:

151990

Hom.:

Cov.:

AF XY:

0.00162

AC XY:

120

AN XY:

74284

show subpopulations

Gnomad4 AFR

AF:

0.00692

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000883

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.0211

Hom.:

2348

Bravo

AF:

0.00231

ESP6500AA

AF:

0.00613

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000626

AC:

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.25

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.079

T;T

Eigen

Uncertain

0.28

Eigen_PC

Benign

0.21

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.75

.;T

MetaRNN

Benign

0.010

T;T

MetaSVM

Benign

-0.84

MutationAssessor

Uncertain

2.5

M;M

PrimateAI

Uncertain

0.63

PROVEAN

Benign

-2.1

N;N

REVEL

Benign

0.25

Sift

Uncertain

0.0020

D;D

Sift4G

Uncertain

0.0020

D;D

Polyphen

0.99

D;D

Vest4

0.61

MutPred

0.73

Loss of MoRF binding (P = 0.0087);Loss of MoRF binding (P = 0.0087);

MVP

0.61

MPC

0.020

ClinPred

0.090

GERP RS

3.6

Varity_R

0.52

gMVP

0.39

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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