22-39244698-C-T

Variant names:

• chr22-39244698-C-T
• rs1800818
• NM_002608.4:c.-735G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 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, PanelApp Australia, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• bilateral striopallidodentate calcinosis

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

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

ENSG00000284633 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
PDGFB	NM_002608.4	c.-735G>A		5_prime_UTR_variant	Exon 1 of 7	ENST00000331163.11	NP_002599.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDGFB	ENST00000331163.11	c.-735G>A		5_prime_UTR_variant	Exon 1 of 7	1	NM_002608.4	ENSP00000330382.6

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

African (AFR) AF: 0.387 AC: 366 AN: 946

American (AMR) AF: 0.751 AC: 505 AN: 672

Ashkenazi Jewish (ASJ) AF: 0.676 AC: 1263 AN: 1868

East Asian (EAS) AF: 0.834 AC: 5080 AN: 6088

South Asian (SAS) AF: 0.721 AC: 186 AN: 258

European-Finnish (FIN) AF: 0.625 AC: 10 AN: 16

Middle Eastern (MID) AF: 0.578 AC: 111 AN: 192

European-Non Finnish (NFE) AF: 0.645 AC: 10915 AN: 16920

Other (OTH) AF: 0.641 AC: 1538 AN: 2398

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

African (AFR) AF: 0.374 AC: 15152 AN: 40560

American (AMR) AF: 0.716 AC: 10716 AN: 14966

Ashkenazi Jewish (ASJ) AF: 0.691 AC: 2377 AN: 3440

East Asian (EAS) AF: 0.902 AC: 4588 AN: 5084

South Asian (SAS) AF: 0.734 AC: 3536 AN: 4820

European-Finnish (FIN) AF: 0.610 AC: 5430 AN: 8900

Middle Eastern (MID) AF: 0.586 AC: 170 AN: 290

European-Non Finnish (NFE) AF: 0.631 AC: 42302 AN: 67076

Other (OTH) AF: 0.601 AC: 1245 AN: 2070

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

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 30, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.94
DANN	Benign	0.95
PhyloP100		-1.8
PromoterAI		-0.00040	Neutral
Mutation Taster		=300/0	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: rs1800818; hg19: chr22-39640703;