8-17621105-A-G

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_001372073.1(PDGFRL):c.408A>G(p.Ala136=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00759 in 1,612,074 control chromosomes in the GnomAD database, including 58 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0061 ( 4 hom., cov: 31)

Exomes 𝑓: 0.0077 ( 54 hom. )

Consequence

PDGFRL
NM_001372073.1 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter U:1B:1

Conservation

PhyloP100: -6.29

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 -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 8-17621105-A-G is Benign according to our data. Variant chr8-17621105-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1048868.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-6.29 with no splicing effect.

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00775 (11308/1459882) while in subpopulation MID AF= 0.0221 (127/5736). AF 95% confidence interval is 0.019. There are 54 homozygotes in gnomad4_exome. There are 5596 alleles in male gnomad4_exome subpopulation. Median coverage is 30. This position pass quality control queck.

BS2

High Homozygotes in GnomAd at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDGFRL	NM_001372073.1 linkuse as main transcript	c.408A>G	p.Ala136=	synonymous_variant	3/6	ENST00000251630.11
PDGFRL	NM_006207.2 linkuse as main transcript	c.408A>G	p.Ala136=	synonymous_variant	4/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
PDGFRL	ENST00000251630.11 linkuse as main transcript	c.408A>G	p.Ala136=	synonymous_variant	3/6	5	NM_001372073.1	P1
PDGFRL	ENST00000541323.1 linkuse as main transcript	c.408A>G	p.Ala136=	synonymous_variant	4/7	2		P1
PDGFRL	ENST00000673645.1 linkuse as main transcript			downstream_gene_variant

Frequencies

GnomAD3 genomes

AF:

0.00609

AC:

926

AN:

152074

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00200

Gnomad AMI

AF:

0.0274

Gnomad AMR

AF:

0.00720

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.000776

Gnomad SAS

AF:

0.00767

Gnomad FIN

AF:

0.000566

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00935

Gnomad OTH

AF:

0.00812

GnomAD3 exomes

AF:

0.00637

AC:

1596

AN:

250448

Hom.:

AF XY:

0.00668

AC XY:

904

AN XY:

135392

show subpopulations

Gnomad AFR exome

AF:

0.00142

Gnomad AMR exome

AF:

0.00657

Gnomad ASJ exome

AF:

0.00268

Gnomad EAS exome

AF:

0.000708

Gnomad SAS exome

AF:

0.00591

Gnomad FIN exome

AF:

0.000647

Gnomad NFE exome

AF:

0.00943

Gnomad OTH exome

AF:

0.00721

GnomAD4 exome

AF:

0.00775

AC:

11308

AN:

1459882

Hom.:

Cov.:

AF XY:

0.00771

AC XY:

5596

AN XY:

726188

show subpopulations

Gnomad4 AFR exome

AF:

0.00147

Gnomad4 AMR exome

AF:

0.00630

Gnomad4 ASJ exome

AF:

0.00172

Gnomad4 EAS exome

AF:

0.000303

Gnomad4 SAS exome

AF:

0.00543

Gnomad4 FIN exome

AF:

0.000955

Gnomad4 NFE exome

AF:

0.00885

Gnomad4 OTH exome

AF:

0.00735

GnomAD4 genome

AF:

0.00610

AC:

929

AN:

152192

Hom.:

Cov.:

AF XY:

0.00563

AC XY:

419

AN XY:

74398

show subpopulations

Gnomad4 AFR

AF:

0.00200

Gnomad4 AMR

AF:

0.00719

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.000778

Gnomad4 SAS

AF:

0.00809

Gnomad4 FIN

AF:

0.000566

Gnomad4 NFE

AF:

0.00935

Gnomad4 OTH

AF:

0.00851

Alfa

AF:

0.00757

Hom.:

Bravo

AF:

0.00612

Asia WGS

AF:

0.00895

AC:

AN:

3478

EpiCase

AF:

0.0104

EpiControl

AF:

0.0112

ClinVar

Significance: Likely benign

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:1

Uncertain significance, no assertion criteria provided	clinical testing	Department of Pathology and Laboratory Medicine, Sinai Health System	-	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Feb 01, 2023	PDGFRL: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

Cadd

Benign

0.075

Dann

Benign

0.23

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

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