4-55082031-G-C

Variant names:

• chr4-55082031-G-C
• NM_002253.4:c.3773C>G

Variant summary

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

The NM_002253.4(KDR):​c.3773C>G​(p.Thr1258Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: KDR NM_002253.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.43

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]

ENSG00000250646 (HGNC:):

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
KDR	NM_002253.4	c.3773C>G	p.Thr1258Arg	missense_variant	Exon 29 of 30	ENST00000263923.5	NP_002244.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KDR	ENST00000263923.5	c.3773C>G	p.Thr1258Arg	missense_variant	Exon 29 of 30	1	NM_002253.4	ENSP00000263923.4
KDR	ENST00000647068.1	n.3786C>G		non_coding_transcript_exon_variant	Exon 29 of 30
ENSG00000250646	ENST00000511222.1	n.233+6789G>C		intron_variant	Intron 3 of 3	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.78
BayesDel_addAF	Pathogenic	0.16	D
BayesDel_noAF	Uncertain	0.0
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.44	T;T
Eigen	Uncertain	0.66
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.76	.;T
M_CAP	Uncertain	0.11	D
MetaRNN	Uncertain	0.53	D;D
MetaSVM	Uncertain	0.019	D
MutationAssessor	Uncertain	2.9	M;M
PrimateAI	Uncertain	0.71	T
PROVEAN	Uncertain	-3.1	.;D
REVEL	Uncertain	0.49
Sift	Uncertain	0.0080	.;D
Sift4G	Uncertain	0.013	.;D
Polyphen		0.85	P;P
Vest4		0.73
MutPred		0.12		Loss of phosphorylation at T1258 (P = 0.0486);Loss of phosphorylation at T1258 (P = 0.0486);
MVP		0.41
MPC		0.21
ClinPred		0.97	D
GERP RS		5.9
Varity_R		0.27
gMVP		0.58

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: chr4-55948198;