5-150115722-AG-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_002609.4(PDGFRB):c.*40del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000624 in 1,518,858 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0031 (1 hom., cov: 33)
  • Exomes 𝑓: 0.00035 (1 hom.)
• Consequence: PDGFRB NM_002609.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.19

Genes affected

PDGFRB (HGNC:8804): (platelet derived growth factor receptor beta) The protein encoded by this gene is a cell surface tyrosine kinase receptor for members of the platelet-derived growth factor family. These growth factors are mitogens for cells of mesenchymal origin. The identity of the growth factor bound to a receptor monomer determines whether the functional receptor is a homodimer (PDGFB or PDGFD) or a heterodimer (PDGFA and PDGFB). This gene is essential for normal development of the cardiovascular system and aids in rearrangement of the actin cytoskeleton. This gene is flanked on chromosome 5 by the genes for granulocyte-macrophage colony-stimulating factor and macrophage-colony stimulating factor receptor; all three genes may be implicated in the 5-q syndrome. A translocation between chromosomes 5 and 12, that fuses this gene to that of the ETV6 gene, results in chronic myeloproliferative disorder with eosinophilia. [provided by RefSeq, Aug 2017]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 5-150115722-AG-A is Benign according to our data. Variant chr5-150115722-AG-A is described in ClinVar as [Likely_benign]. Clinvar id is 1207572.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00308 (469/152208) while in subpopulation AFR AF= 0.0108 (449/41546). AF 95% confidence interval is 0.00998. There are 1 homozygotes in gnomad4. There are 220 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd at 470 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDGFRB	NM_002609.4	c.*40del		3_prime_UTR_variant	23/23	ENST00000261799.9
PDGFRB	NM_001355016.2	c.*40del		3_prime_UTR_variant	22/22
PDGFRB	NM_001355017.2	c.*40del		3_prime_UTR_variant	23/23

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDGFRB	ENST00000261799.9	c.*40del		3_prime_UTR_variant	23/23	1	NM_002609.4	P1
PDGFRB	ENST00000520579.5			downstream_gene_variant		1

Frequencies

GnomAD3 genomes AF: 0.00309 AC: 470 AN: 152090 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.0109

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000458

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000965

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000736

Gnomad OTH AF: 0.00143

GnomAD3 exomes AF: 0.00115 AC: 198 AN: 172104 Hom.: 0 AF XY: 0.000850 AC XY: 79 AN XY: 92940

Gnomad AFR exome AF: 0.0129

Gnomad AMR exome AF: 0.000850

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000398

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000679

Gnomad NFE exome AF: 0.000133

Gnomad OTH exome AF: 0.000258

GnomAD4 exome AF: 0.000350 AC: 479 AN: 1366650 Hom.: 1 Cov.: 29 AF XY: 0.000335 AC XY: 225 AN XY: 671530

Gnomad4 AFR exome AF: 0.0109

Gnomad4 AMR exome AF: 0.000813

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000210

Gnomad4 SAS exome AF: 0.0000277

Gnomad4 FIN exome AF: 0.000170

Gnomad4 NFE exome AF: 0.0000704

Gnomad4 OTH exome AF: 0.000481

GnomAD4 genome AF: 0.00308 AC: 469 AN: 152208 Hom.: 1 Cov.: 33 AF XY: 0.00296 AC XY: 220 AN XY: 74428

Gnomad4 AFR AF: 0.0108

Gnomad4 AMR AF: 0.000458

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000967

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000736

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.000261 Hom.: 0

Bravo AF: 0.00353

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 04, 2019

- -

Computational scores

Source: dbNSFP v4.3

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: rs745433929; hg19: chr5-149495285;