chr22-39225792-G-T

Position:

• chr22-39225792-G-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_002608.4(PDGFB):​c.657C>A​(p.Pro219Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00282 in 1,614,018 control chromosomes in the GnomAD database, including 111 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 (52 hom.)
• Consequence: PDGFB NM_002608.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.288

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP6: Variant 22-39225792-G-T is Benign according to our data. Variant chr22-39225792-G-T is described in ClinVar as [Benign]. Clinvar id is 777710.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-39225792-G-T is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=0.288 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0518 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDGFB	NM_002608.4	c.657C>A	p.Pro219Pro	synonymous_variant	6/7	ENST00000331163.11	NP_002599.1
PDGFB	NM_033016.3	c.612C>A	p.Pro204Pro	synonymous_variant	6/7		NP_148937.1
PDGFB	XM_047441393.1	c.564C>A	p.Pro188Pro	synonymous_variant	6/7		XP_047297349.1
PDGFB	XM_047441394.1	c.564C>A	p.Pro188Pro	synonymous_variant	6/7		XP_047297350.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDGFB	ENST00000331163.11	c.657C>A	p.Pro219Pro	synonymous_variant	6/7	1	NM_002608.4	ENSP00000330382.6
PDGFB	ENST00000381551.8	c.612C>A	p.Pro204Pro	synonymous_variant	6/7	5		ENSP00000370963.4

Frequencies

GnomAD3 genomes AF: 0.0152 AC: 2309 AN: 152160 Hom.: 58 Cov.: 32

Gnomad AFR AF: 0.0538

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: 0.00386 AC: 970 AN: 251272 Hom.: 21 AF XY: 0.00285 AC XY: 387 AN XY: 135824

Gnomad AFR exome AF: 0.0541

Gnomad AMR exome AF: 0.00171

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.0000653

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000194

Gnomad OTH exome AF: 0.00114

GnomAD4 exome AF: 0.00153 AC: 2231 AN: 1461740 Hom.: 52 Cov.: 31 AF XY: 0.00124 AC XY: 902 AN XY: 727170

Gnomad4 AFR exome AF: 0.0559

Gnomad4 AMR exome AF: 0.00197

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.000104

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000612

Gnomad4 OTH exome AF: 0.00306

GnomAD4 genome AF: 0.0152 AC: 2315 AN: 152278 Hom.: 59 Cov.: 32 AF XY: 0.0148 AC XY: 1101 AN XY: 74436

Gnomad4 AFR AF: 0.0537

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: 0.00807 Hom.: 16

Bravo AF: 0.0169

Asia WGS AF: 0.0120 AC: 41 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 01, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 26, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	7.1
DANN	Benign	0.71

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: rs35978693; hg19: chr22-39621797; COSMIC: COSV58648093; COSMIC: COSV58648093;