chr22-39226555-T-C

Position:

• chr22-39226555-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002608.4(PDGFB):​c.602-708A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.372 in 152,118 control chromosomes in the GnomAD database, including 11,061 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.37 (11061 hom., cov: 33)
• Consequence: PDGFB NM_002608.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.663

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.422 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDGFB	NM_002608.4	c.602-708A>G		intron_variant		ENST00000331163.11	NP_002599.1
PDGFB	NM_033016.3	c.557-708A>G		intron_variant			NP_148937.1
PDGFB	XM_047441393.1	c.509-708A>G		intron_variant			XP_047297349.1
PDGFB	XM_047441394.1	c.509-708A>G		intron_variant			XP_047297350.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDGFB	ENST00000331163.11	c.602-708A>G		intron_variant		1	NM_002608.4	ENSP00000330382.6
PDGFB	ENST00000381551.8	c.557-708A>G		intron_variant		5		ENSP00000370963.4

Frequencies

GnomAD3 genomes AF: 0.372 AC: 56583 AN: 152000 Hom.: 11067 Cov.: 33

Gnomad AFR AF: 0.281

Gnomad AMI AF: 0.426

Gnomad AMR AF: 0.341

Gnomad ASJ AF: 0.401

Gnomad EAS AF: 0.181

Gnomad SAS AF: 0.345

Gnomad FIN AF: 0.516

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.426

Gnomad OTH AF: 0.380

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.372 AC: 56587 AN: 152118 Hom.: 11061 Cov.: 33 AF XY: 0.375 AC XY: 27909 AN XY: 74358

Gnomad4 AFR AF: 0.280

Gnomad4 AMR AF: 0.340

Gnomad4 ASJ AF: 0.401

Gnomad4 EAS AF: 0.181

Gnomad4 SAS AF: 0.345

Gnomad4 FIN AF: 0.516

Gnomad4 NFE AF: 0.426

Gnomad4 OTH AF: 0.378

Alfa AF: 0.257 Hom.: 631

Bravo AF: 0.357

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.3
DANN	Benign	0.76

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs2285094; hg19: chr22-39622560;