11-103965969-C-T

Variant names:

• chr11-103965969-C-T
• rs2220377
• NM_025208.5:c.511-18245G>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.511-18245G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.521 in 152,024 control chromosomes in the GnomAD database, including 21,244 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 0.52 (21244 hom., cov: 32)
• Consequence: PDGFD NM_025208.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.22
• Publications: 5 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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.619 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDGFD	NM_025208.5	MANE Select	c.511-18245G>A		intron	N/A	NP_079484.1	Q9GZP0-1
	PDGFD	NM_033135.4		c.493-18245G>A		intron	N/A	NP_149126.1	Q9GZP0-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDGFD	ENST00000393158.7	TSL:1 MANE Select	c.511-18245G>A		intron	N/A	ENSP00000376865.2	Q9GZP0-1
	PDGFD	ENST00000302251.9	TSL:1	c.493-18245G>A		intron	N/A	ENSP00000302193.5	Q9GZP0-2
	PDGFD	ENST00000956141.1		c.511-18226G>A		intron	N/A	ENSP00000626200.1

Frequencies

GnomAD3 genomes AF: 0.521 AC: 79193 AN: 151906 Hom.: 21211 Cov.: 32

Gnomad AFR AF: 0.625

Gnomad AMI AF: 0.361

Gnomad AMR AF: 0.593

Gnomad ASJ AF: 0.468

Gnomad EAS AF: 0.581

Gnomad SAS AF: 0.630

Gnomad FIN AF: 0.462

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.444

Gnomad OTH AF: 0.534

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

GnomAD4 genome AF: 0.521 AC: 79268 AN: 152024 Hom.: 21244 Cov.: 32 AF XY: 0.526 AC XY: 39043 AN XY: 74292

African (AFR) AF: 0.625 AC: 25924 AN: 41474

American (AMR) AF: 0.593 AC: 9056 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.468 AC: 1622 AN: 3468

East Asian (EAS) AF: 0.580 AC: 2990 AN: 5152

South Asian (SAS) AF: 0.629 AC: 3029 AN: 4812

European-Finnish (FIN) AF: 0.462 AC: 4884 AN: 10570

Middle Eastern (MID) AF: 0.469 AC: 138 AN: 294

European-Non Finnish (NFE) AF: 0.444 AC: 30169 AN: 67968

Other (OTH) AF: 0.533 AC: 1128 AN: 2116

Alfa AF: 0.474 Hom.: 47663

Bravo AF: 0.533

Asia WGS AF: 0.625 AC: 2173 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.13
DANN	Benign	0.44
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: rs2220377; hg19: chr11-103836697;