4-55113391-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -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 was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
KDR	NM_002253.4 link	c.889G>A	p.Val297Ile	missense_variant	Exon 7 of 30	ENST00000263923.5	NP_002244.1	P35968-1

Ensembl

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

GnomAD2 exomes

AF:

0.106

AC:

26587

AN:

251324

AF XY:

0.105

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 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

AC:

8011

AN:

33474

Gnomad4 AMR exome

AF:

0.0631

AC:

2821

AN:

44710

Gnomad4 ASJ exome

AF:

0.0994

AC:

2598

AN:

26128

Gnomad4 EAS exome

AF:

0.127

AC:

5039

AN:

39692

Gnomad4 SAS exome

AF:

0.103

AC:

8909

AN:

86258

Gnomad4 FIN exome

AF:

0.0891

AC:

4761

AN:

53418

Gnomad4 NFE exome

AF:

0.0980

AC:

109001

AN:

1111904

Gnomad4 Remaining exome

AF:

0.111

AC:

6699

AN:

60392

Heterozygous variant carriers

7718

15437

23155

30874

38592

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

4108

8216

12324

16432

20540

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

AC:

0.239174

AN:

0.239174

Gnomad4 AMR

AF:

0.0910

AC:

0.0909864

AN:

0.0909864

Gnomad4 ASJ

AF:

0.0994

AC:

0.0994236

AN:

0.0994236

Gnomad4 EAS

AF:

0.143

AC:

0.142581

AN:

0.142581

Gnomad4 SAS

AF:

0.104

AC:

0.10357

AN:

0.10357

Gnomad4 FIN

AF:

0.0865

AC:

0.086513

AN:

0.086513

Gnomad4 NFE

AF:

0.0995

AC:

0.0994677

AN:

0.0994677

Gnomad4 OTH

AF:

0.123

AC:

0.122749

AN:

0.122749

Heterozygous variant carriers

880

1761

2641

3522

4402

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

224

448

672

896

1120

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.111

Hom.:

4787

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

Aug 02, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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

Sep 19, 2013

ITMI

Significance:not provided

Review Status:no classification provided

Collection Method:reference population

- -

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

Mutation Taster

=84/16

polymorphism (auto)

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