Variant 4-55113391-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_002253.4(KDR):c.889G>A(p.Val297Ile) variant causes a missense change. The variant allele was found at a frequency of 0.105 in 1,613,886 control chromosomes in the GnomAD database, including 9,959 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.14 ( 1762 hom., cov: 32)

Exomes 𝑓: 0.10 ( 8197 hom. )

Consequence

KDR
NM_002253.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1O:1

Conservation

PhyloP100: 4.92

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0017504394).

BP6

Variant 4-55113391-C-T is Benign according to our data. Variant chr4-55113391-C-T is described in ClinVar as [Benign]. Clinvar id is 134616.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr4-55113391-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.235 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KDR	NM_002253.4 link	c.889G>A	p.Val297Ile	missense_variant	7/30	ENST00000263923.5	NP_002244.1	P35968-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
KDR	ENST00000263923.5 link	c.889G>A	p.Val297Ile	missense_variant	7/30	1	NM_002253.4	ENSP00000263923.4	P35968-1
KDR	ENST00000512566.1 link	n.889G>A		non_coding_transcript_exon_variant	7/13	1
KDR	ENST00000647068.1 link	n.902G>A		non_coding_transcript_exon_variant	7/30

Frequencies

GnomAD3 genomes

AF:

0.138

AC:

20918

AN:

152026

Hom.:

1757

Cov.:

show subpopulations

Gnomad AFR

AF:

0.239

Gnomad AMI

AF:

0.0789

Gnomad AMR

AF:

0.0910

Gnomad ASJ

AF:

0.0994

Gnomad EAS

AF:

0.142

Gnomad SAS

AF:

0.104

Gnomad FIN

AF:

0.0865

Gnomad MID

AF:

0.133

Gnomad NFE

AF:

0.0995

Gnomad OTH

AF:

0.122

GnomAD3 exomes

AF:

0.106

AC:

26587

AN:

251324

Hom.:

1724

AF XY:

0.105

AC XY:

14258

AN XY:

135832

show subpopulations

Gnomad AFR exome

AF:

0.235

Gnomad AMR exome

AF:

0.0604

Gnomad ASJ exome

AF:

0.105

Gnomad EAS exome

AF:

0.145

Gnomad SAS exome

AF:

0.108

Gnomad FIN exome

AF:

0.0883

Gnomad NFE exome

AF:

0.0979

Gnomad OTH exome

AF:

0.101

GnomAD4 exome

AF:

0.102

AC:

148422

AN:

1461742

Hom.:

8197

Cov.:

AF XY:

0.101

AC XY:

73567

AN XY:

727174

show subpopulations

Gnomad4 AFR exome

AF:

0.239

Gnomad4 AMR exome

AF:

0.0631

Gnomad4 ASJ exome

AF:

0.0994

Gnomad4 EAS exome

AF:

0.127

Gnomad4 SAS exome

AF:

0.103

Gnomad4 FIN exome

AF:

0.0891

Gnomad4 NFE exome

AF:

0.0980

Gnomad4 OTH exome

AF:

0.111

GnomAD4 genome

AF:

0.138

AC:

20945

AN:

152144

Hom.:

1762

Cov.:

AF XY:

0.135

AC XY:

10061

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.239

Gnomad4 AMR

AF:

0.0910

Gnomad4 ASJ

AF:

0.0994

Gnomad4 EAS

AF:

0.143

Gnomad4 SAS

AF:

0.104

Gnomad4 FIN

AF:

0.0865

Gnomad4 NFE

AF:

0.0995

Gnomad4 OTH

AF:

0.123

Alfa

AF:

0.106

Hom.:

2356

Bravo

AF:

0.141

TwinsUK

AF:

0.104

AC:

384

ALSPAC

AF:

0.101

AC:

389

ESP6500AA

AF:

0.223

AC:

984

ESP6500EA

AF:

0.101

AC:

872

ExAC

AF:

0.109

AC:

13217

Asia WGS

AF:

0.158

AC:

549

AN:

3478

EpiCase

AF:

0.0996

EpiControl

AF:

0.0961

ClinVar

Significance: Benign

Submissions summary: Benign:1Other:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

KDR-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 02, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not specified

Other:1

not provided, no classification provided

reference population

ITMI

Sep 19, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.31

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.074

T;T

Eigen

Uncertain

0.38

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.67

.;T

MetaRNN

Benign

0.0018

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

3.0

M;M

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.55

.;N

REVEL

Benign

0.16

Sift

Benign

0.059

.;T

Sift4G

Uncertain

0.052

.;T

Polyphen

1.0

D;D

Vest4

0.11

MPC

0.61

ClinPred

0.033

GERP RS

4.6

Varity_R

0.58

gMVP

0.77

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over