11-103991948-C-T

Variant names:

• chr11-103991948-C-T
• rs17101814
• NM_025208.5:c.510+4117G>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+4117G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0481 in 152,196 control chromosomes in the GnomAD database, including 259 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 0.048 (259 hom., cov: 32)
• Consequence: PDGFD NM_025208.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.682
• Publications: 1 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0953 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDGFD	NM_025208.5	c.510+4117G>A		intron_variant	Intron 3 of 6	ENST00000393158.7	NP_079484.1
PDGFD	NM_033135.4	c.492+4117G>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+4117G>A		intron_variant	Intron 3 of 6	1	NM_025208.5	ENSP00000376865.2
PDGFD	ENST00000302251.9	c.492+4117G>A		intron_variant	Intron 3 of 6	1		ENSP00000302193.5
PDGFD	ENST00000529268.1	c.579+4117G>A		intron_variant	Intron 3 of 3	5		ENSP00000432909.1

Frequencies

GnomAD3 genomes AF: 0.0479 AC: 7290 AN: 152078 Hom.: 258 Cov.: 32

Gnomad AFR AF: 0.0975

Gnomad AMI AF: 0.0746

Gnomad AMR AF: 0.0231

Gnomad ASJ AF: 0.00749

Gnomad EAS AF: 0.0320

Gnomad SAS AF: 0.0334

Gnomad FIN AF: 0.0417

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0285

Gnomad OTH AF: 0.0440

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

GnomAD4 genome AF: 0.0481 AC: 7316 AN: 152196 Hom.: 259 Cov.: 32 AF XY: 0.0473 AC XY: 3519 AN XY: 74400

African (AFR) AF: 0.0978 AC: 4059 AN: 41514

American (AMR) AF: 0.0230 AC: 352 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00749 AC: 26 AN: 3472

East Asian (EAS) AF: 0.0319 AC: 165 AN: 5168

South Asian (SAS) AF: 0.0337 AC: 162 AN: 4810

European-Finnish (FIN) AF: 0.0417 AC: 442 AN: 10592

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0285 AC: 1939 AN: 68038

Other (OTH) AF: 0.0436 AC: 92 AN: 2112

Alfa AF: 0.0438 Hom.: 31

Bravo AF: 0.0490

Asia WGS AF: 0.0310 AC: 110 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.41
DANN	Benign	0.54
PhyloP100		-0.68
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: rs17101814; hg19: chr11-103862676;