11-103943464-G-A

Variant summary

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

The NM_025208.5(PDGFD):​c.760C>T​(p.Arg254Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000325 in 1,611,822 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R254Q) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00034 ( 0 hom. )

Consequence

PDGFD
NM_025208.5 missense

Scores

2
7
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.59
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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 UniProt
PDGFDNM_025208.5 linkuse as main transcriptc.760C>T p.Arg254Trp missense_variant 5/7 ENST00000393158.7
PDGFDNM_033135.4 linkuse as main transcriptc.742C>T p.Arg248Trp missense_variant 5/7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PDGFDENST00000393158.7 linkuse as main transcriptc.760C>T p.Arg254Trp missense_variant 5/71 NM_025208.5 P1Q9GZP0-1
PDGFDENST00000302251.9 linkuse as main transcriptc.742C>T p.Arg248Trp missense_variant 5/71 Q9GZP0-2

Frequencies

GnomAD3 genomes
AF:
0.000197
AC:
30
AN:
152062
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000242
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.0000944
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000412
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000112
AC:
28
AN:
250260
Hom.:
0
AF XY:
0.000118
AC XY:
16
AN XY:
135266
show subpopulations
Gnomad AFR exome
AF:
0.0000616
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0000464
Gnomad NFE exome
AF:
0.000221
Gnomad OTH exome
AF:
0.000164
GnomAD4 exome
AF:
0.000338
AC:
494
AN:
1459642
Hom.:
0
Cov.:
31
AF XY:
0.000315
AC XY:
229
AN XY:
726122
show subpopulations
Gnomad4 AFR exome
AF:
0.0000599
Gnomad4 AMR exome
AF:
0.0000449
Gnomad4 ASJ exome
AF:
0.0000384
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000563
Gnomad4 NFE exome
AF:
0.000420
Gnomad4 OTH exome
AF:
0.000315
GnomAD4 genome
AF:
0.000197
AC:
30
AN:
152180
Hom.:
0
Cov.:
32
AF XY:
0.000134
AC XY:
10
AN XY:
74412
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.0000944
Gnomad4 NFE
AF:
0.000412
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000277
Hom.:
0
Bravo
AF:
0.000170
TwinsUK
AF:
0.000539
AC:
2
ALSPAC
AF:
0.000259
AC:
1
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.000465
AC:
4
ExAC
AF:
0.0000989
AC:
12
EpiCase
AF:
0.000273
EpiControl
AF:
0.0000594

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsMar 01, 2023The c.760C>T (p.R254W) alteration is located in exon 5 (coding exon 5) of the PDGFD gene. This alteration results from a C to T substitution at nucleotide position 760, causing the arginine (R) at amino acid position 254 to be replaced by a tryptophan (W). 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
0.25
BayesDel_addAF
Benign
-0.26
T
BayesDel_noAF
Benign
-0.28
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.47
T;.
Eigen
Uncertain
0.31
Eigen_PC
Benign
0.21
FATHMM_MKL
Benign
0.68
D
LIST_S2
Uncertain
0.96
D;D
M_CAP
Benign
0.053
D
MetaRNN
Uncertain
0.73
D;D
MetaSVM
Benign
-0.82
T
MutationAssessor
Uncertain
2.3
M;.
MutationTaster
Benign
1.0
D;D
PrimateAI
Benign
0.48
T
PROVEAN
Uncertain
-4.0
D;D
REVEL
Benign
0.22
Sift
Pathogenic
0.0
D;D
Sift4G
Pathogenic
0.0010
D;D
Polyphen
1.0
D;D
Vest4
0.68
MVP
0.84
MPC
0.72
ClinPred
0.78
D
GERP RS
2.1
Varity_R
0.46
gMVP
0.78

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs138512366; hg19: chr11-103814192; COSMIC: COSV56387231; COSMIC: COSV56387231; API