chr22-39237617-C-T

Variant names:

• chr22-39237617-C-T
• rs5757573
• NM_002608.4:c.64-1743G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002608.4(PDGFB):​c.64-1743G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.584 in 152,028 control chromosomes in the GnomAD database, including 27,588 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 0.58 (27588 hom., cov: 32)
• Consequence: PDGFB NM_002608.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.515
• Publications: 20 publications found

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]

PDGFB Gene-Disease associations (from GenCC):

• basal ganglia calcification, idiopathic, 5

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Genomics England PanelApp, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• bilateral striopallidodentate calcinosis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• familial meningioma

  Inheritance: AD, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.878 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002608.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDGFB	NM_002608.4	MANE Select	c.64-1743G>A		intron	N/A	NP_002599.1	A0A384NYY3
	PDGFB	NM_033016.3		c.19-1743G>A		intron	N/A	NP_148937.1	P01127-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDGFB	ENST00000331163.11	TSL:1 MANE Select	c.64-1743G>A		intron	N/A	ENSP00000330382.6	P01127-1
	PDGFB	ENST00000971907.1		c.64-1743G>A		intron	N/A	ENSP00000641966.1
	PDGFB	ENST00000921091.1		c.64-1743G>A		intron	N/A	ENSP00000591150.1

Frequencies

GnomAD3 genomes AF: 0.584 AC: 88737 AN: 151910 Hom.: 27586 Cov.: 32

Gnomad AFR AF: 0.376

Gnomad AMI AF: 0.521

Gnomad AMR AF: 0.716

Gnomad ASJ AF: 0.696

Gnomad EAS AF: 0.900

Gnomad SAS AF: 0.738

Gnomad FIN AF: 0.624

Gnomad MID AF: 0.586

Gnomad NFE AF: 0.635

Gnomad OTH AF: 0.597

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

GnomAD4 genome AF: 0.584 AC: 88771 AN: 152028 Hom.: 27588 Cov.: 32 AF XY: 0.591 AC XY: 43914 AN XY: 74308

African (AFR) AF: 0.376 AC: 15582 AN: 41482

American (AMR) AF: 0.717 AC: 10931 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.696 AC: 2416 AN: 3472

East Asian (EAS) AF: 0.900 AC: 4649 AN: 5166

South Asian (SAS) AF: 0.736 AC: 3551 AN: 4822

European-Finnish (FIN) AF: 0.624 AC: 6593 AN: 10566

Middle Eastern (MID) AF: 0.582 AC: 170 AN: 292

European-Non Finnish (NFE) AF: 0.635 AC: 43145 AN: 67958

Other (OTH) AF: 0.598 AC: 1260 AN: 2108

Alfa AF: 0.610 Hom.: 60720

Bravo AF: 0.581

Asia WGS AF: 0.793 AC: 2757 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.6
DANN	Benign	0.82
PhyloP100		-0.52
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs5757573; hg19: chr22-39633622;