Variant 8-17589661-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_001372073.1(PDGFRL):c.249C>A(p.Thr83Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00206 in 1,613,248 control chromosomes in the GnomAD database, including 74 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.011 ( 40 hom., cov: 31)

Exomes 𝑓: 0.0011 ( 34 hom. )

Consequence

PDGFRL
NM_001372073.1 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.273

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.23).

BP6

Variant 8-17589661-C-A is Benign according to our data. Variant chr8-17589661-C-A is described in ClinVar as [Benign]. Clinvar id is 714376.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.273 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0109 (1652/152248) while in subpopulation AFR AF= 0.0381 (1580/41522). AF 95% confidence interval is 0.0365. There are 40 homozygotes in gnomad4. There are 732 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 40 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDGFRL	NM_001372073.1 linkuse as main transcript	c.249C>A	p.Thr83Thr	synonymous_variant	2/6	ENST00000251630.11	NP_001359002.1
PDGFRL	NM_006207.2 linkuse as main transcript	c.249C>A	p.Thr83Thr	synonymous_variant	3/7		NP_006198.1	Q15198

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PDGFRL	ENST00000251630.11 linkuse as main transcript	c.249C>A	p.Thr83Thr	synonymous_variant	2/6	5	NM_001372073.1	ENSP00000251630.4	Q15198
PDGFRL	ENST00000541323.1 linkuse as main transcript	c.249C>A	p.Thr83Thr	synonymous_variant	3/7	2		ENSP00000444211.1	Q15198
PDGFRL	ENST00000673645.1 linkuse as main transcript	c.249C>A	p.Thr83Thr	synonymous_variant	3/4			ENSP00000501219.1	A0A669KBD1

Frequencies

GnomAD3 genomes

AF:

0.0108

AC:

1649

AN:

152130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0381

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00294

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.00718

GnomAD3 exomes

AF:

0.00283

AC:

711

AN:

251362

Hom.:

AF XY:

0.00214

AC XY:

291

AN XY:

135886

show subpopulations

Gnomad AFR exome

AF:

0.0389

Gnomad AMR exome

AF:

0.00179

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000704

Gnomad OTH exome

AF:

0.00114

GnomAD4 exome

AF:

0.00114

AC:

1672

AN:

1461000

Hom.:

Cov.:

AF XY:

0.000993

AC XY:

722

AN XY:

726846

show subpopulations

Gnomad4 AFR exome

AF:

0.0409

Gnomad4 AMR exome

AF:

0.00201

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000666

Gnomad4 OTH exome

AF:

0.00212

GnomAD4 genome

AF:

0.0109

AC:

1652

AN:

152248

Hom.:

Cov.:

AF XY:

0.00983

AC XY:

732

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.0381

Gnomad4 AMR

AF:

0.00294

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.00711

Alfa

AF:

0.00428

Hom.:

Bravo

AF:

0.0122

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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

BayesDel_noAF

Benign

-0.23

CADD

Benign

2.4

DANN

Benign

0.61

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