rs17110944

Variant names:

• chr5-150135834-T-A
• rs17110944
• NM_002609.4:c.85A>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002609.4(PDGFRB):​c.85A>T​(p.Ile29Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0179 in 1,547,842 control chromosomes in the GnomAD database, including 2,111 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.068 (1000 hom., cov: 33)
  • Exomes 𝑓: 0.012 (1111 hom.)
• Consequence: PDGFRB NM_002609.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 0.173
• Publications: 20 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: 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: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• basal ganglia calcification, idiopathic, 4

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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0034821332).
• BP6: Variant 5-150135834-T-A is Benign according to our data. Variant chr5-150135834-T-A is described in ClinVar as Benign. ClinVar VariationId is 258780.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.206 is higher than 0.05.

Variant Effect in Transcripts

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

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDGFRB	NM_002609.4	MANE Select	c.85A>T	p.Ile29Phe	missense	Exon 3 of 23	NP_002600.1
	PDGFRB	NM_001355016.2		c.-108A>T		5_prime_UTR	Exon 2 of 22	NP_001341945.1
	PDGFRB	NM_001355017.2		c.-433A>T		5_prime_UTR	Exon 3 of 23	NP_001341946.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDGFRB	ENST00000261799.9	TSL:1 MANE Select	c.85A>T	p.Ile29Phe	missense	Exon 3 of 23	ENSP00000261799.4
	PDGFRB	ENST00000520579.5	TSL:1	n.85A>T		non_coding_transcript_exon	Exon 3 of 23	ENSP00000430026.1
	PDGFRB	ENST00000890716.1		c.85A>T	p.Ile29Phe	missense	Exon 3 of 24	ENSP00000560775.1

Frequencies

GnomAD3 genomes AF: 0.0680 AC: 10334 AN: 152020 Hom.: 990 Cov.: 33

Gnomad AFR AF: 0.210

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0558

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0362

Gnomad SAS AF: 0.0606

Gnomad FIN AF: 0.0143

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00137

Gnomad OTH AF: 0.0402

GnomAD2 exomes AF: 0.0381 AC: 7455 AN: 195908 AF XY: 0.0315

Gnomad AFR exome AF: 0.213

Gnomad AMR exome AF: 0.0880

Gnomad ASJ exome AF: 0.000199

Gnomad EAS exome AF: 0.0316

Gnomad FIN exome AF: 0.0156

Gnomad NFE exome AF: 0.00127

Gnomad OTH exome AF: 0.0219

GnomAD4 exome AF: 0.0124 AC: 17254 AN: 1395704 Hom.: 1111 Cov.: 32 AF XY: 0.0125 AC XY: 8603 AN XY: 687500

African (AFR) AF: 0.215 AC: 6706 AN: 31166

American (AMR) AF: 0.0837 AC: 2915 AN: 34822

Ashkenazi Jewish (ASJ) AF: 0.0000922 AC: 2 AN: 21698

East Asian (EAS) AF: 0.0246 AC: 961 AN: 38992

South Asian (SAS) AF: 0.0501 AC: 3741 AN: 74736

European-Finnish (FIN) AF: 0.0155 AC: 788 AN: 50964

Middle Eastern (MID) AF: 0.00901 AC: 49 AN: 5440

European-Non Finnish (NFE) AF: 0.000697 AC: 753 AN: 1080378

Other (OTH) AF: 0.0233 AC: 1339 AN: 57508

GnomAD4 genome AF: 0.0682 AC: 10383 AN: 152138 Hom.: 1000 Cov.: 33 AF XY: 0.0671 AC XY: 4990 AN XY: 74380

African (AFR) AF: 0.210 AC: 8711 AN: 41470

American (AMR) AF: 0.0561 AC: 858 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.0363 AC: 188 AN: 5180

South Asian (SAS) AF: 0.0600 AC: 289 AN: 4816

European-Finnish (FIN) AF: 0.0143 AC: 152 AN: 10600

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00137 AC: 93 AN: 68006

Other (OTH) AF: 0.0431 AC: 91 AN: 2110

Alfa AF: 0.0295 Hom.: 85

Bravo AF: 0.0770

TwinsUK AF: 0.00135 AC: 5

ALSPAC AF: 0.000778 AC: 3

ESP6500AA AF: 0.212 AC: 933

ESP6500EA AF: 0.000814 AC: 7

ExAC AF: 0.0377 AC: 4561

Asia WGS AF: 0.0750 AC: 260 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	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 (1)
-	-	1	Myeloproliferative disorder, chronic, with eosinophilia (1)
-	-	1	Myofibromatosis, infantile, 1 (1)
-	-	1	PDGFRB-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	0.66
DANN	Benign	0.73
DEOGEN2	Benign	0.26	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.092	N
LIST_S2	Benign	0.52	T
MetaRNN	Benign	0.0035	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.34	N
PhyloP100		0.17
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.81	N
REVEL	Benign	0.019
Sift	Benign	0.33	T
Sift4G	Benign	0.42	T
Polyphen		0.022	B
Vest4		0.059
MPC		0.36
ClinPred		0.00030	T
GERP RS		-1.5
Varity_R		0.060
gMVP		0.29
Mutation Taster		=97/3	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: rs17110944; hg19: chr5-149515397; COSMIC: COSV55802660; COSMIC: COSV55802660;