4-55110507-G-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_002253.4(KDR):​c.1151C>A​(p.Thr384Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000123 in 1,461,704 control chromosomes in the GnomAD database, with no homozygous occurrence. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

KDR
NM_002253.4 missense

Scores

5
14

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.80
Variant links:
Genes affected
KDR (HGNC:6307): (kinase insert domain receptor) Vascular endothelial growth factor (VEGF) is a major growth factor for endothelial cells. This gene encodes one of the two receptors of the VEGF. This receptor, known as kinase insert domain receptor, is a type III receptor tyrosine kinase. It functions as the main mediator of VEGF-induced endothelial proliferation, survival, migration, tubular morphogenesis and sprouting. The signalling and trafficking of this receptor are regulated by multiple factors, including Rab GTPase, P2Y purine nucleotide receptor, integrin alphaVbeta3, T-cell protein tyrosine phosphatase, etc.. Mutations of this gene are implicated in infantile capillary hemangiomas. [provided by RefSeq, May 2009]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2
High AC in GnomAdExome4 at 18 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
KDRNM_002253.4 linkc.1151C>A p.Thr384Lys missense_variant Exon 9 of 30 ENST00000263923.5 NP_002244.1 P35968-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
KDRENST00000263923.5 linkc.1151C>A p.Thr384Lys missense_variant Exon 9 of 30 1 NM_002253.4 ENSP00000263923.4 P35968-1
KDRENST00000512566.1 linkn.1151C>A non_coding_transcript_exon_variant Exon 9 of 13 1
KDRENST00000647068.1 linkn.1164C>A non_coding_transcript_exon_variant Exon 9 of 30

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.0000123
AC:
18
AN:
1461704
Hom.:
0
Cov.:
33
AF XY:
0.0000138
AC XY:
10
AN XY:
727174
show subpopulations
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:
0.0000153
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.19
BayesDel_addAF
Uncertain
0.099
D
BayesDel_noAF
Benign
-0.10
CADD
Benign
17
DANN
Benign
0.97
DEOGEN2
Benign
0.15
T;T
Eigen
Benign
-0.12
Eigen_PC
Benign
-0.14
FATHMM_MKL
Uncertain
0.91
D
LIST_S2
Benign
0.69
.;T
M_CAP
Benign
0.067
D
MetaRNN
Uncertain
0.57
D;D
MetaSVM
Benign
-0.55
T
MutationAssessor
Benign
1.5
L;L
PrimateAI
Benign
0.32
T
PROVEAN
Benign
-1.8
.;N
REVEL
Uncertain
0.42
Sift
Uncertain
0.022
.;D
Sift4G
Benign
0.064
.;T
Polyphen
0.77
P;P
Vest4
0.44
MutPred
0.73
Gain of ubiquitination at T384 (P = 0.017);Gain of ubiquitination at T384 (P = 0.017);
MVP
0.55
MPC
0.48
ClinPred
0.69
D
GERP RS
4.8
Varity_R
0.31
gMVP
0.76

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: chr4-55976674; API