NM_002609.4:c.2362_2364delCGAinsGGG

Variant names:

• chr5-150121303-TCG-CCC
• NM_002609.4:c.2362_2364delCGAinsGGG
• PDGFRB p.Arg788Gly

GermlineCancer (beta)

Variant summary

Our verdict is Uncertain significance.

+2 Uncertain · Warm

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received 2 classification points (ACMG Germline Pathogenicity v2019). PM2

The NM_002609.4(PDGFRB):c.2362_2364delCGAinsGGG (p.Arg788Gly) variant causes a missense change. Note: allele frequency estimates from gnomAD may be inaccurate for this variant type (MNP or indel longer than 3 bp) due to technology limitations. The variant is absent from the gnomAD population database at sites with sufficient sequencing coverage. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Other variants at the same amino acid position have been reported in ClinVar (not pathogenic): p.R788*: Uncertain_significance (ClinVar VariationId 520866, 2 stars)

• Frequency: Genomes: not found (cov: 32)
• Consequence: PDGFRB NM_002609.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.73
• Publications: 0 publications found

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]

PDGFRB Gene-Disease associations (from GenCC):

• acroosteolysis-keloid-like lesions-premature aging syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: PanelApp Australia, G2P, Orphanet, Labcorp Genetics (formerly Invitae)
• myofibromatosis, infantile, 1

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• skeletal overgrowth-craniofacial dysmorphism-hyperelastic skin-white matter lesions syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia
• basal ganglia calcification, idiopathic, 4

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

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• infantile myofibromatosis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• hereditary progressive mucinous histiocytosis

  Inheritance: AD Classification: LIMITED Submitted by: G2P
• ocular pterygium-digital keloid dysplasia syndrome

  Inheritance: AD Classification: LIMITED Submitted by: PanelApp Australia

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript:

Our verdict: Uncertain_significance. The variant received 2 points.

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	PM2Absent/extremely low in population databases		Absent from gnomAD (AD/XL gene) — PM2; Absent from gnomAD at well-covered site (MOI: AD/XL) (threshold 0.0001) — PM2 moderate.

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_002609.4. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	PDGFRB NM_002609.4	MANE Select	c.2362_2364delCGAinsGGG p.Arg788Gly	missense	N/A	Prot: NP_002600.1 UniProt:
	PDGFRB NM_001355016.2		c.2170_2172delCGAinsGGG p.Arg724Gly	missense	N/A	Prot: NP_001341945.1
	PDGFRB NM_001355017.2		c.1879_1881delCGAinsGGG p.Arg627Gly	missense	N/A	Prot: NP_001341946.1

PDGFRB NM_002609.4

MANE Select

HGVSc / HGVSpc.2362_2364delCGAinsGGGp.Arg788Gly

Exon rankN/A

missense

Prot: NP_002600.1UniProt: P09619-1

PDGFRB NM_001355016.2

HGVSc / HGVSpc.2170_2172delCGAinsGGGp.Arg724Gly

Exon rankN/A

missense

Prot: NP_001341945.1

PDGFRB NM_001355017.2

HGVSc / HGVSpc.1879_1881delCGAinsGGGp.Arg627Gly

Exon rankN/A

missense

Prot: NP_001341946.1

Ensembl Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	PDGFRB ENST00000261799.9	TSL:1MANE Select	c.2362_2364delCGAinsGGG p.Arg788Gly	missense	N/A	Prot: ENSP00000261799.4 UniProt:
	PDGFRB ENST00000520579.5	TSL:1	n.*1676_*1678delCGAinsGGG	3_prime_UTR	Exon 17 of 23	Prot: ENSP00000430026.1 UniProt:
	PDGFRB ENST00000520579.5	TSL:1	n.*1676_*1678delCGAinsGGG	non_coding_transcript_exon	Exon 17 of 23	Prot: ENSP00000430026.1 UniProt:

PDGFRB ENST00000261799.9

TSL:1MANE Select

HGVSc / HGVSpc.2362_2364delCGAinsGGGp.Arg788Gly

Exon rankN/A

missense

Prot: ENSP00000261799.4UniProt: P09619-1

PDGFRB ENST00000520579.5

TSL:1

HGVSc / HGVSpn.*1676_*1678delCGAinsGGG

Exon rankExon 17 of 23

3_prime_UTR

Prot: ENSP00000430026.1UniProt: E5RH16

PDGFRB ENST00000520579.5

TSL:1

HGVSc / HGVSpn.*1676_*1678delCGAinsGGG

Exon rankExon 17 of 23

non_coding_transcript_exon

Prot: ENSP00000430026.1UniProt: E5RH16

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)

Rare (AF ≤ 0.0001 / Hom ≤ 1)

Source / population	AF	AC	Hom	AN	Coverage
Global population databases 2 sources Large-scale international reference populations
GnomAD3 genomes	AF:	AC:	Hom:	AN:	Cov:32
GnomAD4 genome	AF:	AC:	Hom:	AN:	Cov:32

Showing 2 sources

Tested, but no data found:GnomAD4 exomeIf GnomAD4 is missing, the position is probably not covered by the project.

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
PhyloP100	Benign	2.7

Showing 1 of 1 scores

Splicing Scores

No splicing scores have been computed for this variant.

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

MaveDB functional evidence

MaveDB is a public repository of laboratory assays that test the effect of thousands of variants at once — treat this as supporting research data and interpret it with great caution; it is not a clinical classification.

No MaveDB functional evidence found for this variant.

Other links and lift over

hg19: chr5-149500866;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar