22-39225699-CCA-C

Position:

• chr22-39225699-CCA-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_002608.4(PDGFB):​c.*22_*23del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00282 in 1,610,292 control chromosomes in the GnomAD database, including 111 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.015 (59 hom., cov: 31)
  • Exomes 𝑓: 0.0015 (52 hom.)
• Consequence: PDGFB NM_002608.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.00

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 -10 ACMG points.

• BP6: Variant 22-39225699-CCA-C is Benign according to our data. Variant chr22-39225699-CCA-C is described in ClinVar as [Benign]. Clinvar id is 1226480.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0519 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDGFB	NM_002608.4	c.*22_*23del		3_prime_UTR_variant	6/7	ENST00000331163.11
PDGFB	NM_033016.3	c.*22_*23del		3_prime_UTR_variant	6/7
PDGFB	XM_047441393.1	c.*22_*23del		3_prime_UTR_variant	6/7
PDGFB	XM_047441394.1	c.*22_*23del		3_prime_UTR_variant	6/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDGFB	ENST00000331163.11	c.*22_*23del		3_prime_UTR_variant	6/7	1	NM_002608.4	P1
PDGFB	ENST00000381551.8	c.*22_*23del		3_prime_UTR_variant	6/7	5

Frequencies

GnomAD3 genomes AF: 0.0152 AC: 2314 AN: 152098 Hom.: 58 Cov.: 31

Gnomad AFR AF: 0.0539

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: 0.00949

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00956

GnomAD3 exomes AF: 0.00387 AC: 965 AN: 249594 Hom.: 20 AF XY: 0.00286 AC XY: 386 AN XY: 134928

Gnomad AFR exome AF: 0.0539

Gnomad AMR exome AF: 0.00172

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000546

Gnomad SAS exome AF: 0.0000656

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000195

Gnomad OTH exome AF: 0.00115

GnomAD4 exome AF: 0.00153 AC: 2224 AN: 1458076 Hom.: 52 AF XY: 0.00125 AC XY: 903 AN XY: 725042

Gnomad4 AFR exome AF: 0.0559

Gnomad4 AMR exome AF: 0.00198

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000105

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000613

Gnomad4 OTH exome AF: 0.00305

GnomAD4 genome AF: 0.0152 AC: 2320 AN: 152216 Hom.: 59 Cov.: 31 AF XY: 0.0149 AC XY: 1105 AN XY: 74408

Gnomad4 AFR AF: 0.0538

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: 0.0118

Alfa AF: 0.00799 Hom.: 7

Bravo AF: 0.0169

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

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: rs35677215; hg19: chr22-39621704;