chr22-39225779-G-A

Position:

chr22-39225779-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_002608.4(PDGFB):c.670C>T(p.Arg224Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00149 in 1,614,008 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00088 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0016 ( 4 hom. )

Consequence

PDGFB
NM_002608.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts U:1B:2

Conservation

PhyloP100: 2.74

Variant links:

Genes affected

PDGFB (HGNC:8800): (platelet derived growth factor subunit B) This gene encodes a member of the protein family comprised of both platelet-derived growth factors (PDGF) and vascular endothelial growth factors (VEGF). The encoded preproprotein is proteolytically processed to generate platelet-derived growth factor subunit B, which can homodimerize, or alternatively, heterodimerize with the related platelet-derived growth factor subunit A. These proteins bind and activate PDGF receptor tyrosine kinases, which play a role in a wide range of developmental processes. Mutations in this gene are associated with meningioma. Reciprocal translocations between chromosomes 22 and 17, at sites where this gene and that for collagen type 1, alpha 1 are located, are associated with dermatofibrosarcoma protuberans, a rare skin tumor. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2015]

PDGFB links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.054261923).

BP6

Variant 22-39225779-G-A is Benign according to our data. Variant chr22-39225779-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 522278.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00088 (134/152190) while in subpopulation NFE AF= 0.00172 (117/68030). AF 95% confidence interval is 0.00147. There are 1 homozygotes in gnomad4. There are 66 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 134 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
PDGFB	NM_002608.4 linkuse as main transcript	c.670C>T	p.Arg224Trp	missense_variant	6/7	ENST00000331163.11
PDGFB	NM_033016.3 linkuse as main transcript	c.625C>T	p.Arg209Trp	missense_variant	6/7
PDGFB	XM_047441393.1 linkuse as main transcript	c.577C>T	p.Arg193Trp	missense_variant	6/7
PDGFB	XM_047441394.1 linkuse as main transcript	c.577C>T	p.Arg193Trp	missense_variant	6/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDGFB	ENST00000331163.11 linkuse as main transcript	c.670C>T	p.Arg224Trp	missense_variant	6/7	1	NM_002608.4	P1	P01127-1
PDGFB	ENST00000381551.8 linkuse as main transcript	c.625C>T	p.Arg209Trp	missense_variant	6/7	5			P01127-2

Frequencies

GnomAD3 genomes

AF:

0.000880

AC:

134

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000362

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00172

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000836

AC:

210

AN:

251286

Hom.:

AF XY:

0.000854

AC XY:

116

AN XY:

135836

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.000174

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.00170

Gnomad OTH exome

AF:

0.000816

GnomAD4 exome

AF:

0.00156

AC:

2274

AN:

1461818

Hom.:

Cov.:

AF XY:

0.00152

AC XY:

1103

AN XY:

727210

show subpopulations

Gnomad4 AFR exome

AF:

0.000418

Gnomad4 AMR exome

AF:

0.000157

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.0000936

Gnomad4 NFE exome

AF:

0.00197

Gnomad4 OTH exome

AF:

0.000861

GnomAD4 genome

AF:

0.000880

AC:

134

AN:

152190

Hom.:

Cov.:

AF XY:

0.000888

AC XY:

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.000362

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.00172

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00140

Hom.:

Bravo

AF:

0.000835

TwinsUK

AF:

0.00297

AC:

ALSPAC

AF:

0.00208

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00174

AC:

ExAC

AF:

0.000758

AC:

EpiCase

AF:

0.00120

EpiControl

AF:

0.00207

ClinVar

Significance: Benign/Likely benign

Submissions summary: Uncertain:1Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 12, 2019	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 18, 2024	- -

Dermatofibrosarcoma protuberans

Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Feb 09, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.26

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.68

D;.

Eigen

Uncertain

0.28

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Benign

0.73

LIST_S2

Uncertain

0.95

D;D

M_CAP

Benign

0.025

MetaRNN

Benign

0.054

T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.8

L;.

MutationTaster

Benign

0.97

D;D

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-2.2

N;N

REVEL

Benign

0.18

Sift

Pathogenic

0.0

D;D

Sift4G

Uncertain

0.0040

D;D

Polyphen

0.99

D;.

Vest4

0.57

MVP

0.50

MPC

0.84

ClinPred

0.085

GERP RS

4.3

Varity_R

0.20

gMVP

0.50

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