22-39231645-G-C

Variant names:

• chr22-39231645-G-C
• NM_002608.4:c.433C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002608.4(PDGFB):​c.433C>G​(p.Gln145Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000014 in 1,425,166 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: PDGFB NM_002608.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.09

Genes affected

PDGFB (HGNC:8800): (platelet derived growth factor subunit B) This gene encodes a member of the protein family comprised of both platelet-derived growth factors (PDGF) and vascular endothelial growth factors (VEGF). The encoded preproprotein is proteolytically processed to generate platelet-derived growth factor subunit B, which can homodimerize, or alternatively, heterodimerize with the related platelet-derived growth factor subunit A. These proteins bind and activate PDGF receptor tyrosine kinases, which play a role in a wide range of developmental processes. Mutations in this gene are associated with meningioma. Reciprocal translocations between chromosomes 22 and 17, at sites where this gene and that for collagen type 1, alpha 1 are located, are associated with dermatofibrosarcoma protuberans, a rare skin tumor. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2015]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18051872).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDGFB	NM_002608.4	c.433C>G	p.Gln145Glu	missense_variant	Exon 4 of 7	ENST00000331163.11	NP_002599.1
PDGFB	NM_033016.3	c.388C>G	p.Gln130Glu	missense_variant	Exon 4 of 7		NP_148937.1
PDGFB	XM_047441393.1	c.340C>G	p.Gln114Glu	missense_variant	Exon 4 of 7		XP_047297349.1
PDGFB	XM_047441394.1	c.340C>G	p.Gln114Glu	missense_variant	Exon 4 of 7		XP_047297350.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDGFB	ENST00000331163.11	c.433C>G	p.Gln145Glu	missense_variant	Exon 4 of 7	1	NM_002608.4	ENSP00000330382.6
PDGFB	ENST00000381551.8	c.388C>G	p.Gln130Glu	missense_variant	Exon 4 of 7	5		ENSP00000370963.4
PDGFB	ENST00000455790.5	c.340C>G	p.Gln114Glu	missense_variant	Exon 4 of 5	4		ENSP00000402306.1
PDGFB	ENST00000440375.1	c.340C>G	p.Gln114Glu	missense_variant	Exon 4 of 5	4		ENSP00000405780.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000140 AC: 2 AN: 1425166 Hom.: 0 Cov.: 31 AF XY: 0.00000142 AC XY: 1 AN XY: 705746

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000245

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.66	D;.;.;T
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.18
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Uncertain	0.89	D;D;D;D
M_CAP	Benign	0.0077	T
MetaRNN	Benign	0.18	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L;.;.;.
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-1.3	N;N;N;N
REVEL	Benign	0.046
Sift	Benign	0.062	T;T;T;T
Sift4G	Benign	0.69	T;T;.;T
Polyphen		0.40	B;.;.;.
Vest4		0.39
MutPred		0.29		Loss of MoRF binding (P = 0.0396);.;.;.;
MVP		0.52
MPC		0.47
ClinPred		0.27	T
GERP RS		3.0
Varity_R		0.51
gMVP		0.64

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-39627650;