chr22-39225574-G-A

Position:

• chr22-39225574-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002608.4(PDGFB):​c.*28+121C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00364 in 981,232 control chromosomes in the GnomAD database, including 88 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.015 (59 hom., cov: 32)
  • Exomes 𝑓: 0.0015 (29 hom.)
• Consequence: PDGFB NM_002608.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.112

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 22-39225574-G-A is Benign according to our data. Variant chr22-39225574-G-A is described in ClinVar as [Benign]. Clinvar id is 1266971.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0522 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDGFB	NM_002608.4	c.*28+121C>T		intron_variant		ENST00000331163.11
PDGFB	NM_033016.3	c.*28+121C>T		intron_variant
PDGFB	XM_047441393.1	c.*28+121C>T		intron_variant
PDGFB	XM_047441394.1	c.*28+121C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDGFB	ENST00000331163.11	c.*28+121C>T		intron_variant		1	NM_002608.4	P1
PDGFB	ENST00000381551.8	c.*28+121C>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.0153 AC: 2321 AN: 152018 Hom.: 58 Cov.: 32

Gnomad AFR AF: 0.0542

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00340

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00955

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00962

GnomAD4 exome AF: 0.00150 AC: 1246 AN: 829096 Hom.: 29 AF XY: 0.00125 AC XY: 523 AN XY: 417290

Gnomad4 AFR exome AF: 0.0534

Gnomad4 AMR exome AF: 0.00227

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000952

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000506

Gnomad4 OTH exome AF: 0.00307

GnomAD4 genome AF: 0.0153 AC: 2327 AN: 152136 Hom.: 59 Cov.: 32 AF XY: 0.0149 AC XY: 1109 AN XY: 74342

Gnomad4 AFR AF: 0.0540

Gnomad4 AMR AF: 0.00340

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000735

Gnomad4 OTH AF: 0.0119

Alfa AF: 0.0122 Hom.: 7

Bravo AF: 0.0170

Asia WGS AF: 0.0120 AC: 41 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 01, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.79
DANN	Benign	0.22

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

Other links and lift over

dbSNP: rs113867122; hg19: chr22-39621579;