Variant 4-55080024-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_002253.4(KDR):c.3988A>T(p.Ile1330Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000465 in 1,614,160 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0026 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00025 ( 1 hom. )

Consequence

KDR
NM_002253.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0160

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:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0038380027).

BP6

Variant 4-55080024-T-A is Benign according to our data. Variant chr4-55080024-T-A is described in ClinVar as [Benign]. Clinvar id is 3040151.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 390 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KDR	NM_002253.4 linkuse as main transcript	c.3988A>T	p.Ile1330Leu	missense_variant	30/30	ENST00000263923.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KDR	ENST00000263923.5 linkuse as main transcript	c.3988A>T	p.Ile1330Leu	missense_variant	30/30	1	NM_002253.4	P1	P35968-1
	ENST00000511222.1 linkuse as main transcript	n.233+4782T>A		intron_variant, non_coding_transcript_variant		5
KDR	ENST00000647068.1 linkuse as main transcript	n.4001A>T		non_coding_transcript_exon_variant	30/30

Frequencies

GnomAD3 genomes

AF:

0.00252

AC:

384

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00859

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00151

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.000724

AC:

182

AN:

251458

Hom.:

AF XY:

0.000456

AC XY:

AN XY:

135896

show subpopulations

Gnomad AFR exome

AF:

0.00917

Gnomad AMR exome

AF:

0.000809

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000440

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000246

AC:

360

AN:

1461888

Hom.:

Cov.:

AF XY:

0.000208

AC XY:

151

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.00809

Gnomad4 AMR exome

AF:

0.000827

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:

0.0000117

Gnomad4 OTH exome

AF:

0.000580

GnomAD4 genome

AF:

0.00256

AC:

390

AN:

152272

Hom.:

Cov.:

AF XY:

0.00259

AC XY:

193

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.00871

Gnomad4 AMR

AF:

0.00150

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000146

Hom.:

Bravo

AF:

0.00288

ESP6500AA

AF:

0.00931

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000865

AC:

105

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

KDR-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 10, 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). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.56

CADD

Benign

0.49

DANN

Benign

0.70

DEOGEN2

Benign

0.066

T;T

Eigen

Benign

-0.94

Eigen_PC

Benign

-0.86

FATHMM_MKL

Benign

0.36

M_CAP

Benign

0.026

MetaRNN

Benign

0.0038

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.77

N;N

MutationTaster

Benign

1.0

PrimateAI

Benign

0.30

Polyphen

0.0

B;B

Vest4

0.077

MutPred

0.25

Loss of methylation at K1328 (P = 0.0522);Loss of methylation at K1328 (P = 0.0522);

MVP

0.068

MPC

0.059

ClinPred

0.00020

GERP RS

0.50

Varity_R

0.053

gMVP

0.11

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