rs17708515

Variant names:

• chr5-150135817-G-A
• rs17708515
• NM_002609.4:c.102C>T

Your query was ambiguous. Multiple possible variants found:

• chr5-150135817-G-A
• chr5-150135817-G-C
• chr5-150135817-G-T

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_001355016.2(PDGFRB):​c.-91C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00742 in 1,579,558 control chromosomes in the GnomAD database, including 401 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.011 (49 hom., cov: 33)
  • Exomes 𝑓: 0.0070 (352 hom.)
• Consequence: PDGFRB NM_001355016.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.989
• Publications: 7 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• basal ganglia calcification, idiopathic, 4

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: 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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BP6: Variant 5-150135817-G-A is Benign according to our data. Variant chr5-150135817-G-A is described in ClinVar as Benign. ClinVar VariationId is 473399.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0537 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001355016.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDGFRB	NM_002609.4	MANE Select	c.102C>T	p.Val34Val	synonymous	Exon 3 of 23	NP_002600.1	P09619-1
	PDGFRB	NM_001355016.2		c.-91C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 22	NP_001341945.1
	PDGFRB	NM_001355017.2		c.-416C>T		5_prime_UTR_premature_start_codon_gain	Exon 3 of 23	NP_001341946.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDGFRB	ENST00000261799.9	TSL:1 MANE Select	c.102C>T	p.Val34Val	synonymous	Exon 3 of 23	ENSP00000261799.4	P09619-1
	PDGFRB	ENST00000520579.5	TSL:1	n.102C>T		non_coding_transcript_exon	Exon 3 of 23	ENSP00000430026.1	E5RH16
	PDGFRB	ENST00000517488.1	TSL:3	c.-91C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 3	ENSP00000429218.1	E5RJ14

Frequencies

GnomAD3 genomes AF: 0.0109 AC: 1656 AN: 152170 Hom.: 43 Cov.: 33

Gnomad AFR AF: 0.00956

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0366

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0360

Gnomad SAS AF: 0.0599

Gnomad FIN AF: 0.0141

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000838

Gnomad OTH AF: 0.00767

GnomAD2 exomes AF: 0.0212 AC: 4649 AN: 219058 AF XY: 0.0198

Gnomad AFR exome AF: 0.00875

Gnomad AMR exome AF: 0.0776

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0306

Gnomad FIN exome AF: 0.0152

Gnomad NFE exome AF: 0.000901

Gnomad OTH exome AF: 0.0142

GnomAD4 exome AF: 0.00703 AC: 10030 AN: 1427270 Hom.: 352 Cov.: 32 AF XY: 0.00793 AC XY: 5606 AN XY: 706806

African (AFR) AF: 0.00938 AC: 304 AN: 32400

American (AMR) AF: 0.0723 AC: 2898 AN: 40086

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23626

East Asian (EAS) AF: 0.0245 AC: 961 AN: 39304

South Asian (SAS) AF: 0.0497 AC: 3964 AN: 79762

European-Finnish (FIN) AF: 0.0154 AC: 803 AN: 52128

Middle Eastern (MID) AF: 0.00305 AC: 17 AN: 5576

European-Non Finnish (NFE) AF: 0.000381 AC: 417 AN: 1095476

Other (OTH) AF: 0.0113 AC: 666 AN: 58912

GnomAD4 genome AF: 0.0111 AC: 1683 AN: 152288 Hom.: 49 Cov.: 33 AF XY: 0.0125 AC XY: 934 AN XY: 74458

African (AFR) AF: 0.00991 AC: 412 AN: 41558

American (AMR) AF: 0.0371 AC: 567 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.0361 AC: 187 AN: 5182

South Asian (SAS) AF: 0.0593 AC: 286 AN: 4820

European-Finnish (FIN) AF: 0.0141 AC: 150 AN: 10624

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

European-Non Finnish (NFE) AF: 0.000838 AC: 57 AN: 68020

Other (OTH) AF: 0.0109 AC: 23 AN: 2108

Alfa AF: 0.00386 Hom.: 8

Bravo AF: 0.0125

Asia WGS AF: 0.0630 AC: 219 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	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	not provided (1)
-	-	1	PDGFRB-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	13
DANN	Benign	0.81
PhyloP100		0.99
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs17708515; hg19: chr5-149515380; COSMIC: COSV55802652; COSMIC: COSV55802652;