rs10895556

Variant names:

• chr11-103990111-T-C
• rs10895556
• NM_025208.5:c.510+5954A>G

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+5954A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 152,162 control chromosomes in the GnomAD database, including 1,381 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 0.12 (1381 hom., cov: 31)
• Consequence: PDGFD NM_025208.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.187
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.162 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.510+5954A>G		intron	N/A	NP_079484.1	Q9GZP0-1
	PDGFD	NM_033135.4		c.492+5954A>G		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.510+5954A>G		intron	N/A	ENSP00000376865.2	Q9GZP0-1
	PDGFD	ENST00000302251.9	TSL:1	c.492+5954A>G		intron	N/A	ENSP00000302193.5	Q9GZP0-2
	PDGFD	ENST00000956141.1		c.510+5954A>G		intron	N/A	ENSP00000626200.1

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18591 AN: 152044 Hom.: 1381 Cov.: 31

Gnomad AFR AF: 0.0496

Gnomad AMI AF: 0.242

Gnomad AMR AF: 0.123

Gnomad ASJ AF: 0.194

Gnomad EAS AF: 0.0697

Gnomad SAS AF: 0.167

Gnomad FIN AF: 0.101

Gnomad MID AF: 0.182

Gnomad NFE AF: 0.164

Gnomad OTH AF: 0.141

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

GnomAD4 genome AF: 0.122 AC: 18591 AN: 152162 Hom.: 1381 Cov.: 31 AF XY: 0.120 AC XY: 8903 AN XY: 74388

African (AFR) AF: 0.0495 AC: 2056 AN: 41512

American (AMR) AF: 0.123 AC: 1881 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.194 AC: 674 AN: 3470

East Asian (EAS) AF: 0.0699 AC: 361 AN: 5168

South Asian (SAS) AF: 0.168 AC: 811 AN: 4816

European-Finnish (FIN) AF: 0.101 AC: 1072 AN: 10600

Middle Eastern (MID) AF: 0.182 AC: 53 AN: 292

European-Non Finnish (NFE) AF: 0.164 AC: 11169 AN: 67992

Other (OTH) AF: 0.139 AC: 294 AN: 2114

Alfa AF: 0.134 Hom.: 228

Bravo AF: 0.120

Asia WGS AF: 0.0960 AC: 335 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.3
DANN	Benign	0.65
PhyloP100		-0.19
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: rs10895556; hg19: chr11-103860839;