11-103987393-C-T

Variant names:

• chr11-103987393-C-T
• rs1872902
• NM_025208.5:c.510+8672G>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+8672G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 151,940 control chromosomes in the GnomAD database, including 6,387 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 0.27 (6387 hom., cov: 31)
• Consequence: PDGFD NM_025208.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.03
• Publications: 6 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.447 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDGFD	NM_025208.5	c.510+8672G>A		intron_variant	Intron 3 of 6	ENST00000393158.7	NP_079484.1
PDGFD	NM_033135.4	c.492+8672G>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+8672G>A		intron_variant	Intron 3 of 6	1	NM_025208.5	ENSP00000376865.2
PDGFD	ENST00000302251.9	c.492+8672G>A		intron_variant	Intron 3 of 6	1		ENSP00000302193.5
PDGFD	ENST00000529268.1	c.579+8672G>A		intron_variant	Intron 3 of 3	5		ENSP00000432909.1

Frequencies

GnomAD3 genomes AF: 0.271 AC: 41168 AN: 151822 Hom.: 6376 Cov.: 31

Gnomad AFR AF: 0.138

Gnomad AMI AF: 0.186

Gnomad AMR AF: 0.439

Gnomad ASJ AF: 0.271

Gnomad EAS AF: 0.462

Gnomad SAS AF: 0.341

Gnomad FIN AF: 0.330

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.287

Gnomad OTH AF: 0.291

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

GnomAD4 genome AF: 0.271 AC: 41196 AN: 151940 Hom.: 6387 Cov.: 31 AF XY: 0.277 AC XY: 20564 AN XY: 74242

African (AFR) AF: 0.138 AC: 5727 AN: 41454

American (AMR) AF: 0.439 AC: 6696 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.271 AC: 940 AN: 3470

East Asian (EAS) AF: 0.462 AC: 2383 AN: 5156

South Asian (SAS) AF: 0.341 AC: 1642 AN: 4810

European-Finnish (FIN) AF: 0.330 AC: 3485 AN: 10552

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.287 AC: 19495 AN: 67934

Other (OTH) AF: 0.293 AC: 618 AN: 2112

Alfa AF: 0.281 Hom.: 10752

Bravo AF: 0.273

Asia WGS AF: 0.392 AC: 1365 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.27
DANN	Benign	0.38
PhyloP100		-1.0
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: rs1872902; hg19: chr11-103858121;