Variant 4-55082630-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_002253.4(KDR):c.3668A>G(p.Tyr1223Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,458,864 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

KDR
NM_002253.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.84

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]

KDR links:

ENSG00000250646 (HGNC:):

ENSG00000250646 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.38835767).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KDR	NM_002253.4 link	c.3668A>G	p.Tyr1223Cys	missense_variant	28/30	ENST00000263923.5	NP_002244.1	P35968-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
KDR	ENST00000263923.5 link	c.3668A>G	p.Tyr1223Cys	missense_variant	28/30	1	NM_002253.4	ENSP00000263923.4	P35968-1
KDR	ENST00000647068.1 link	n.3681A>G		non_coding_transcript_exon_variant	28/30
ENSG00000250646	ENST00000511222.1 link	n.233+7388T>C		intron_variant		5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1458864

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725966

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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 submitter

clinical testing

Ambry Genetics

Dec 17, 2023

The c.3668A>G (p.Y1223C) alteration is located in exon 28 (coding exon 28) of the KDR gene. This alteration results from a A to G substitution at nucleotide position 3668, causing the tyrosine (Y) at amino acid position 1223 to be replaced by a cysteine (C). 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

0.12

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Uncertain

-0.060

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.048

T;T

Eigen

Uncertain

0.36

Eigen_PC

Uncertain

0.43

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.85

.;T

M_CAP

Benign

0.040

MetaRNN

Benign

0.39

T;T

MetaSVM

Benign

-0.45

MutationAssessor

Benign

0.85

L;L

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-0.070

.;N

REVEL

Uncertain

0.32

Sift

Benign

0.27

.;T

Sift4G

Benign

0.19

.;T

Polyphen

0.86

P;P

Vest4

0.72

MutPred

0.46

Loss of phosphorylation at Y1223 (P = 0.026);Loss of phosphorylation at Y1223 (P = 0.026);

MVP

0.30

MPC

0.19

ClinPred

0.66

GERP RS

5.6

Varity_R

0.11

gMVP

0.30

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over