chr11-103937424-C-T

Variant names:

• chr11-103937424-C-T
• rs10895547
• NM_025208.5:c.772+6028G>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.772+6028G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.322 in 151,902 control chromosomes in the GnomAD database, including 8,247 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 (8247 hom., cov: 31)
• Consequence: PDGFD NM_025208.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.255
• Publications: 17 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.377 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDGFD	NM_025208.5	c.772+6028G>A		intron_variant	Intron 5 of 6	ENST00000393158.7	NP_079484.1
PDGFD	NM_033135.4	c.754+6028G>A		intron_variant	Intron 5 of 6		NP_149126.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDGFD	ENST00000393158.7	c.772+6028G>A		intron_variant	Intron 5 of 6	1	NM_025208.5	ENSP00000376865.2
PDGFD	ENST00000302251.9	c.754+6028G>A		intron_variant	Intron 5 of 6	1		ENSP00000302193.5

Frequencies

GnomAD3 genomes AF: 0.322 AC: 48878 AN: 151784 Hom.: 8252 Cov.: 31

Gnomad AFR AF: 0.235

Gnomad AMI AF: 0.356

Gnomad AMR AF: 0.266

Gnomad ASJ AF: 0.325

Gnomad EAS AF: 0.392

Gnomad SAS AF: 0.383

Gnomad FIN AF: 0.372

Gnomad MID AF: 0.360

Gnomad NFE AF: 0.370

Gnomad OTH AF: 0.321

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

GnomAD4 genome AF: 0.322 AC: 48886 AN: 151902 Hom.: 8247 Cov.: 31 AF XY: 0.322 AC XY: 23895 AN XY: 74228

African (AFR) AF: 0.235 AC: 9730 AN: 41432

American (AMR) AF: 0.265 AC: 4045 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.325 AC: 1128 AN: 3468

East Asian (EAS) AF: 0.391 AC: 2016 AN: 5152

South Asian (SAS) AF: 0.383 AC: 1844 AN: 4820

European-Finnish (FIN) AF: 0.372 AC: 3918 AN: 10520

Middle Eastern (MID) AF: 0.356 AC: 104 AN: 292

European-Non Finnish (NFE) AF: 0.370 AC: 25108 AN: 67932

Other (OTH) AF: 0.317 AC: 669 AN: 2110

Alfa AF: 0.352 Hom.: 22977

Bravo AF: 0.310

Asia WGS AF: 0.323 AC: 1122 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.33
DANN	Benign	0.35
PhyloP100		-0.26
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: rs10895547; hg19: chr11-103808152;