5-150115827-A-AGCTCCG

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_002609.4(PDGFRB):c.3256_3257insCGGAGC(p.Pro1084_Glu1085dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: PDGFRB NM_002609.4 inframe_insertion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.840

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDGFRB	NM_002609.4	c.3256_3257insCGGAGC	p.Pro1084_Glu1085dup	inframe_insertion	23/23	ENST00000261799.9
PDGFRB	NM_001355016.2	c.3064_3065insCGGAGC	p.Pro1020_Glu1021dup	inframe_insertion	22/22
PDGFRB	NM_001355017.2	c.2773_2774insCGGAGC	p.Pro923_Glu924dup	inframe_insertion	23/23

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDGFRB	ENST00000261799.9	c.3256_3257insCGGAGC	p.Pro1084_Glu1085dup	inframe_insertion	23/23	1	NM_002609.4	P1
PDGFRB	ENST00000520579.5	c.*2570_*2571insCGGAGC		3_prime_UTR_variant, NMD_transcript_variant	23/23	1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Infantile myofibromatosis;C1866182:Acroosteolysis-keloid-like lesions-premature aging syndrome;C3554321:Basal ganglia calcification, idiopathic, 4;C4225270:Skeletal overgrowth-craniofacial dysmorphism-hyperelastic skin-white matter lesions syndrome Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Invitae

Sep 13, 2023

This variant, c.3256_3257insCGGAGC, results in the insertion of 2 amino acid(s) of the PDGFRB protein (p.Pro1084_Glu1085dup), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with PDGFRB-related conditions. ClinVar contains an entry for this variant (Variation ID: 1999371). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1238695788; hg19: chr5-149495390;