22-39244698-C-T

Position:

• chr22-39244698-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002608.4(PDGFB):​c.-735G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.597 in 177,472 control chromosomes in the GnomAD database, including 33,495 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.58 (26528 hom., cov: 30)
  • Exomes 𝑓: 0.68 (6967 hom.)
• Consequence: PDGFB NM_002608.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.75

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]

ENSG00000284633 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 22-39244698-C-T is Benign according to our data. Variant chr22-39244698-C-T is described in ClinVar as [Benign]. Clinvar id is 1256642.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.881 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDGFB	NM_002608.4	c.-735G>A		5_prime_UTR_variant	1/7	ENST00000331163.11	NP_002599.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDGFB	ENST00000331163.11	c.-735G>A		5_prime_UTR_variant	1/7	1	NM_002608.4	ENSP00000330382.6
ENSG00000284633	ENST00000641466.2	n.75+2402C>T		intron_variant
ENSG00000284633	ENST00000641859.1	n.109+2402C>T		intron_variant
ENSG00000284633	ENST00000692616.2	n.51-1358C>T		intron_variant

Frequencies

GnomAD3 genomes AF: 0.581 AC: 85958 AN: 148022 Hom.: 26531 Cov.: 30

Gnomad AFR AF: 0.374

Gnomad AMI AF: 0.511

Gnomad AMR AF: 0.715

Gnomad ASJ AF: 0.691

Gnomad EAS AF: 0.903

Gnomad SAS AF: 0.735

Gnomad FIN AF: 0.610

Gnomad MID AF: 0.590

Gnomad NFE AF: 0.631

Gnomad OTH AF: 0.601

GnomAD4 exome AF: 0.680 AC: 19974 AN: 29358 Hom.: 6967 Cov.: 0 AF XY: 0.678 AC XY: 9191 AN XY: 13554

Gnomad4 AFR exome AF: 0.387

Gnomad4 AMR exome AF: 0.751

Gnomad4 ASJ exome AF: 0.676

Gnomad4 EAS exome AF: 0.834

Gnomad4 SAS exome AF: 0.721

Gnomad4 FIN exome AF: 0.625

Gnomad4 NFE exome AF: 0.645

Gnomad4 OTH exome AF: 0.641

GnomAD4 genome AF: 0.580 AC: 85980 AN: 148114 Hom.: 26528 Cov.: 30 AF XY: 0.587 AC XY: 42440 AN XY: 72306

Gnomad4 AFR AF: 0.374

Gnomad4 AMR AF: 0.716

Gnomad4 ASJ AF: 0.691

Gnomad4 EAS AF: 0.902

Gnomad4 SAS AF: 0.734

Gnomad4 FIN AF: 0.610

Gnomad4 NFE AF: 0.631

Gnomad4 OTH AF: 0.601

Alfa AF: 0.478 Hom.: 1434

Bravo AF: 0.578

Asia WGS AF: 0.785 AC: 2692 AN: 3432

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 30, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.94
DANN	Benign	0.95

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: rs1800818; hg19: chr22-39640703;