11-104000057-A-T

Variant names:

• chr11-104000057-A-T
• rs1025498191
• NM_025208.5:c.323T>A

Variant summary

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

The NM_025208.5(PDGFD):​c.323T>A​(p.Ile108Asn) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I108T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: PDGFD NM_025208.5 missense
• Clinical Significance: Not reported in ClinVar
• 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 rank	MANE	Protein	UniProt
PDGFD	NM_025208.5	c.323T>A	p.Ile108Asn	missense_variant	Exon 2 of 7	ENST00000393158.7	NP_079484.1
PDGFD	NM_033135.4	c.305T>A	p.Ile102Asn	missense_variant	Exon 2 of 7		NP_149126.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDGFD	ENST00000393158.7	c.323T>A	p.Ile108Asn	missense_variant	Exon 2 of 7	1	NM_025208.5	ENSP00000376865.2
PDGFD	ENST00000302251.9	c.305T>A	p.Ile102Asn	missense_variant	Exon 2 of 7	1		ENSP00000302193.5
PDGFD	ENST00000529268.1	c.392T>A	p.Ile131Asn	missense_variant	Exon 2 of 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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.52
BayesDel_addAF	Benign	-0.083	T
BayesDel_noAF	Benign	-0.36
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.28	T;.;.
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.97	D;D;D
M_CAP	Benign	0.018	T
MetaRNN	Uncertain	0.65	D;D;D
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.23	N;.;.
PrimateAI	Uncertain	0.62	T
PROVEAN	Uncertain	-3.9	D;D;D
REVEL	Uncertain	0.45
Sift	Uncertain	0.025	D;D;D
Sift4G	Pathogenic	0.0010	D;D;.
Polyphen		1.0	D;D;.
Vest4		0.67
MutPred		0.55		Gain of disorder (P = 0.0171);.;.;
MVP		0.79
MPC		1.0
ClinPred		0.99	D
GERP RS		5.5
Varity_R		0.58
gMVP		0.65

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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;