11-104105565-C-T

Variant names:

• chr11-104105565-C-T
• rs488753
• NM_025208.5:c.124+58239G>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.124+58239G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.603 in 151,756 control chromosomes in the GnomAD database, including 28,125 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 0.60 (28125 hom., cov: 31)
• Consequence: PDGFD NM_025208.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.23
• Publications: 7 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.792 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025208.5. 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
	PDGFD	NM_025208.5	MANE Select	c.124+58239G>A		intron	N/A	NP_079484.1
	PDGFD	NM_033135.4		c.124+58239G>A		intron	N/A	NP_149126.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDGFD	ENST00000393158.7	TSL:1 MANE Select	c.124+58239G>A		intron	N/A	ENSP00000376865.2
	PDGFD	ENST00000302251.9	TSL:1	c.124+58239G>A		intron	N/A	ENSP00000302193.5

Frequencies

GnomAD3 genomes AF: 0.603 AC: 91467 AN: 151636 Hom.: 28116 Cov.: 31

Gnomad AFR AF: 0.499

Gnomad AMI AF: 0.611

Gnomad AMR AF: 0.685

Gnomad ASJ AF: 0.443

Gnomad EAS AF: 0.812

Gnomad SAS AF: 0.736

Gnomad FIN AF: 0.682

Gnomad MID AF: 0.436

Gnomad NFE AF: 0.620

Gnomad OTH AF: 0.574

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

GnomAD4 genome AF: 0.603 AC: 91524 AN: 151756 Hom.: 28125 Cov.: 31 AF XY: 0.610 AC XY: 45264 AN XY: 74156

African (AFR) AF: 0.498 AC: 20603 AN: 41330

American (AMR) AF: 0.686 AC: 10430 AN: 15206

Ashkenazi Jewish (ASJ) AF: 0.443 AC: 1539 AN: 3472

East Asian (EAS) AF: 0.813 AC: 4201 AN: 5170

South Asian (SAS) AF: 0.735 AC: 3532 AN: 4804

European-Finnish (FIN) AF: 0.682 AC: 7187 AN: 10534

Middle Eastern (MID) AF: 0.438 AC: 128 AN: 292

European-Non Finnish (NFE) AF: 0.620 AC: 42136 AN: 67932

Other (OTH) AF: 0.575 AC: 1213 AN: 2108

Alfa AF: 0.607 Hom.: 119268

Bravo AF: 0.593

Asia WGS AF: 0.719 AC: 2498 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.47
DANN	Benign	0.74
PhyloP100		-1.2
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: rs488753; hg19: chr11-103976293;