rs12574463

Variant names:

• chr11-103994015-C-T
• rs12574463
• NM_025208.5:c.510+2050G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_025208.5(PDGFD):​c.510+2050G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 152,064 control chromosomes in the GnomAD database, including 2,203 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.17 (2203 hom., cov: 32)
• Consequence: PDGFD NM_025208.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.14
• Publications: 4 publications found

Genes affected

PDGFD (HGNC:30620): (platelet derived growth factor D) The protein encoded by this gene is a member of the platelet-derived growth factor family. The four members of this family are mitogenic factors for cells of mesenchymal origin and are characterized by a core motif of eight cysteines, seven of which are found in this factor. This gene product only forms homodimers and, therefore, does not dimerize with the other three family members. It differs from alpha and beta members of this family in having an unusual N-terminal domain, the CUB domain. Two splice variants have been identified for this gene. [provided by RefSeq, Jul 2008]

PDGFD Gene-Disease associations (from GenCC):

• pulmonary arterial hypertension

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.197 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDGFD	NM_025208.5	c.510+2050G>A		intron_variant	Intron 3 of 6	ENST00000393158.7	NP_079484.1
PDGFD	NM_033135.4	c.492+2050G>A		intron_variant	Intron 3 of 6		NP_149126.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDGFD	ENST00000393158.7	c.510+2050G>A		intron_variant	Intron 3 of 6	1	NM_025208.5	ENSP00000376865.2
PDGFD	ENST00000302251.9	c.492+2050G>A		intron_variant	Intron 3 of 6	1		ENSP00000302193.5
PDGFD	ENST00000529268.1	c.579+2050G>A		intron_variant	Intron 3 of 3	5		ENSP00000432909.1

Frequencies

GnomAD3 genomes AF: 0.165 AC: 25144 AN: 151950 Hom.: 2201 Cov.: 32

Gnomad AFR AF: 0.200

Gnomad AMI AF: 0.231

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.189

Gnomad EAS AF: 0.0712

Gnomad SAS AF: 0.177

Gnomad FIN AF: 0.140

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.159

Gnomad OTH AF: 0.165

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.165 AC: 25163 AN: 152064 Hom.: 2203 Cov.: 32 AF XY: 0.163 AC XY: 12090 AN XY: 74330

African (AFR) AF: 0.200 AC: 8299 AN: 41462

American (AMR) AF: 0.136 AC: 2074 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.189 AC: 655 AN: 3468

East Asian (EAS) AF: 0.0712 AC: 369 AN: 5186

South Asian (SAS) AF: 0.177 AC: 855 AN: 4820

European-Finnish (FIN) AF: 0.140 AC: 1474 AN: 10552

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.159 AC: 10830 AN: 67974

Other (OTH) AF: 0.163 AC: 343 AN: 2108

Alfa AF: 0.164 Hom.: 8870

Bravo AF: 0.165

Asia WGS AF: 0.107 AC: 372 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.0
DANN	Benign	0.46
PhyloP100		1.1
Mutation Taster		=100/0	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: rs12574463; hg19: chr11-103864743;