chr11-104160870-C-G

Variant names:

• chr11-104160870-C-G
• rs7950273
• NM_025208.5:c.124+2934G>C

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+2934G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.321 in 152,022 control chromosomes in the GnomAD database, including 7,891 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 0.32 (7891 hom., cov: 31)
• Consequence: PDGFD NM_025208.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.69
• Publications: 8 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.364 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDGFD	NM_025208.5	c.124+2934G>C		intron_variant	Intron 1 of 6	ENST00000393158.7	NP_079484.1
PDGFD	NM_033135.4	c.124+2934G>C		intron_variant	Intron 1 of 6		NP_149126.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDGFD	ENST00000393158.7	c.124+2934G>C		intron_variant	Intron 1 of 6	1	NM_025208.5	ENSP00000376865.2
PDGFD	ENST00000302251.9	c.124+2934G>C		intron_variant	Intron 1 of 6	1		ENSP00000302193.5

Frequencies

GnomAD3 genomes AF: 0.321 AC: 48711 AN: 151904 Hom.: 7888 Cov.: 31

Gnomad AFR AF: 0.369

Gnomad AMI AF: 0.357

Gnomad AMR AF: 0.317

Gnomad ASJ AF: 0.288

Gnomad EAS AF: 0.318

Gnomad SAS AF: 0.214

Gnomad FIN AF: 0.342

Gnomad MID AF: 0.382

Gnomad NFE AF: 0.298

Gnomad OTH AF: 0.311

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

GnomAD4 genome AF: 0.321 AC: 48742 AN: 152022 Hom.: 7891 Cov.: 31 AF XY: 0.321 AC XY: 23888 AN XY: 74316

African (AFR) AF: 0.368 AC: 15265 AN: 41430

American (AMR) AF: 0.317 AC: 4853 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.288 AC: 997 AN: 3466

East Asian (EAS) AF: 0.319 AC: 1644 AN: 5160

South Asian (SAS) AF: 0.215 AC: 1034 AN: 4818

European-Finnish (FIN) AF: 0.342 AC: 3610 AN: 10562

Middle Eastern (MID) AF: 0.373 AC: 109 AN: 292

European-Non Finnish (NFE) AF: 0.298 AC: 20252 AN: 67978

Other (OTH) AF: 0.309 AC: 652 AN: 2112

Alfa AF: 0.321 Hom.: 975

Bravo AF: 0.324

Asia WGS AF: 0.269 AC: 936 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.036
DANN	Benign	0.32
PhyloP100		-1.7
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: rs7950273; hg19: chr11-104031598;