rs2228439
Positions:
Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2
The NM_002609.4(PDGFRB):āc.1149G>Cā(p.Leu383=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0104 in 1,606,436 control chromosomes in the GnomAD database, including 108 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: š 0.0077 ( 5 hom., cov: 32)
Exomes š: 0.011 ( 103 hom. )
Consequence
PDGFRB
NM_002609.4 synonymous
NM_002609.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.593
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -19 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.43).
BP6
?
Variant 5-150132073-C-G is Benign according to our data. Variant chr5-150132073-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 473400.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-150132073-C-G is described in Lovd as [Benign]. Variant chr5-150132073-C-G is described in Lovd as [Likely_benign].
BP7
?
Synonymous conserved (PhyloP=0.593 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00775 (1180/152310) while in subpopulation NFE AF= 0.0116 (790/68026). AF 95% confidence interval is 0.0109. There are 5 homozygotes in gnomad4. There are 543 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd4 at 1180 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PDGFRB | NM_002609.4 | c.1149G>C | p.Leu383= | synonymous_variant | 8/23 | ENST00000261799.9 | |
PDGFRB | NM_001355016.2 | c.957G>C | p.Leu319= | synonymous_variant | 7/22 | ||
PDGFRB | NM_001355017.2 | c.666G>C | p.Leu222= | synonymous_variant | 8/23 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PDGFRB | ENST00000261799.9 | c.1149G>C | p.Leu383= | synonymous_variant | 8/23 | 1 | NM_002609.4 | P1 | |
PDGFRB | ENST00000520579.5 | c.*463G>C | 3_prime_UTR_variant, NMD_transcript_variant | 8/23 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.00775 AC: 1180AN: 152192Hom.: 5 Cov.: 32
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GnomAD3 exomes AF: 0.00777 AC: 1948AN: 250762Hom.: 13 AF XY: 0.00770 AC XY: 1044AN XY: 135544
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GnomAD4 exome AF: 0.0107 AC: 15524AN: 1454126Hom.: 103 Cov.: 28 AF XY: 0.0104 AC XY: 7516AN XY: 723928
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GnomAD4 genome ? AF: 0.00775 AC: 1180AN: 152310Hom.: 5 Cov.: 32 AF XY: 0.00729 AC XY: 543AN XY: 74474
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:8
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:3
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jan 01, 2024 | PDGFRB: BP4, BP7, BS1, BS2 - |
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 12, 2021 | - - |
not specified Benign:2
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, Amsterdam University Medical Center | - | - - |
PDGFRB-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jul 02, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Myeloproliferative disorder, chronic, with eosinophilia Benign:1
Benign, criteria provided, single submitter | clinical testing | KCCC/NGS Laboratory, Kuwait Cancer Control Center | Jul 07, 2023 | - - |
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 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 26, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at