11-103996218-T-C

Variant names:

• chr11-103996218-T-C
• NM_025208.5:c.357A>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_025208.5(PDGFD):​c.357A>G​(p.Ile119Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PDGFD NM_025208.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.211

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15627456).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDGFD	NM_025208.5	c.357A>G	p.Ile119Met	missense_variant	Exon 3 of 7	ENST00000393158.7	NP_079484.1
PDGFD	NM_033135.4	c.339A>G	p.Ile113Met	missense_variant	Exon 3 of 7		NP_149126.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDGFD	ENST00000393158.7	c.357A>G	p.Ile119Met	missense_variant	Exon 3 of 7	1	NM_025208.5	ENSP00000376865.2
PDGFD	ENST00000302251.9	c.339A>G	p.Ile113Met	missense_variant	Exon 3 of 7	1		ENSP00000302193.5
PDGFD	ENST00000529268.1	c.426A>G	p.Ile142Met	missense_variant	Exon 3 of 4	5		ENSP00000432909.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 20, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.357A>G (p.I119M) alteration is located in exon 3 (coding exon 3) of the PDGFD gene. This alteration results from a A to G substitution at nucleotide position 357, causing the isoleucine (I) at amino acid position 119 to be replaced by a methionine (M). 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	Benign	0.11
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	12
DANN	Benign	0.95
DEOGEN2	Benign	0.080	T;.;.
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.32
FATHMM_MKL	Benign	0.55	D
LIST_S2	Benign	0.63	T;T;T
M_CAP	Benign	0.0073	T
MetaRNN	Benign	0.16	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L;.;.
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.11	N;N;N
REVEL	Benign	0.052
Sift	Benign	0.15	T;T;T
Sift4G	Benign	0.12	T;T;.
Polyphen		0.43	B;P;.
Vest4		0.34
MutPred		0.49		Gain of catalytic residue at I119 (P = 0.0151);.;.;
MVP		0.55
MPC		0.49
ClinPred		0.16	T
GERP RS		1.9
Varity_R		0.053
gMVP		0.50

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-103866946;