11-104000057-A-G

Position:

• chr11-104000057-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_025208.5(PDGFD):​c.323T>C​(p.Ile108Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,610 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: PDGFD NM_025208.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.90

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDGFD	NM_025208.5	c.323T>C	p.Ile108Thr	missense_variant	2/7	ENST00000393158.7	NP_079484.1
PDGFD	NM_033135.4	c.305T>C	p.Ile102Thr	missense_variant	2/7		NP_149126.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDGFD	ENST00000393158.7	c.323T>C	p.Ile108Thr	missense_variant	2/7	1	NM_025208.5	ENSP00000376865.2
PDGFD	ENST00000302251.9	c.305T>C	p.Ile102Thr	missense_variant	2/7	1		ENSP00000302193.5
PDGFD	ENST00000529268.1	c.392T>C	p.Ile131Thr	missense_variant	2/4	5		ENSP00000432909.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461610 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727112

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 16, 2022

The c.323T>C (p.I108T) alteration is located in exon 2 (coding exon 2) of the PDGFD gene. This alteration results from a T to C substitution at nucleotide position 323, causing the isoleucine (I) at amino acid position 108 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.48
BayesDel_addAF	Benign	-0.090	T
BayesDel_noAF	Benign	-0.37
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T;.;.
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.91	D;D;D
M_CAP	Benign	0.0087	T
MetaRNN	Uncertain	0.44	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.29	N;.;.
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-2.2	N;N;D
REVEL	Benign	0.21
Sift	Benign	0.088	T;T;T
Sift4G	Benign	0.094	T;T;.
Polyphen		0.96	D;P;.
Vest4		0.61
MutPred		0.49		Loss of stability (P = 0.0266);.;.;
MVP		0.84
MPC		0.78
ClinPred		0.94	D
GERP RS		5.5
Varity_R		0.19
gMVP		0.55

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

Publications

LitVar

Other links and lift over

dbSNP: rs1025498191; hg19: chr11-103870785;