rs34038364

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_002253.4(KDR):c.2066C>T(p.Thr689Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00332 in 1,613,602 control chromosomes in the GnomAD database, including 13 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 0.0029 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0034 ( 12 hom. )

Consequence

KDR
NM_002253.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts U:1B:3O:1

Conservation

PhyloP100: -0.0930

Publications

15 publications found

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 Gene-Disease associations (from GenCC):

pulmonary arterial hypertension
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen

KDR links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0052033663).

BP6

Variant 4-55102430-G-A is Benign according to our data. Variant chr4-55102430-G-A is described in ClinVar as Benign. ClinVar VariationId is 134606.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 443 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002253.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KDR	NM_002253.4	MANE Select	c.2066C>T	p.Thr689Met	missense	Exon 14 of 30	NP_002244.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KDR	ENST00000263923.5	TSL:1 MANE Select	c.2066C>T	p.Thr689Met	missense	Exon 14 of 30	ENSP00000263923.4
	KDR	ENST00000647068.1		n.2079C>T		non_coding_transcript_exon	Exon 14 of 30

Frequencies

GnomAD3 genomes

AF:

0.00291

AC:

443

AN:

152138

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000772

Gnomad AMI

AF:

0.00548

Gnomad AMR

AF:

0.00242

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0138

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00322

Gnomad OTH

AF:

0.00191

GnomAD2 exomes

AF:

0.00319

AC:

800

AN:

251160

AF XY:

0.00297

show subpopulations

Gnomad AFR exome

AF:

0.000738

Gnomad AMR exome

AF:

0.00258

Gnomad ASJ exome

AF:

0.0000993

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0152

Gnomad NFE exome

AF:

0.00296

Gnomad OTH exome

AF:

0.00523

GnomAD4 exome

AF:

0.00336

AC:

4916

AN:

1461346

Hom.:

Cov.:

AF XY:

0.00322

AC XY:

2344

AN XY:

726994

show subpopulations

African (AFR)

AF:

0.000389

AC:

AN:

33446

American (AMR)

AF:

0.00242

AC:

108

AN:

44700

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26118

East Asian (EAS)

AF:

0.00

AC:

AN:

39688

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.0136

AC:

724

AN:

53418

Middle Eastern (MID)

AF:

0.000347

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

0.00349

AC:

3880

AN:

1111600

Other (OTH)

AF:

0.00310

AC:

187

AN:

60364

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

261

523

784

1046

1307

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

150

300

450

600

750

<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:

0.00291

AC:

443

AN:

152256

Hom.:

Cov.:

AF XY:

0.00353

AC XY:

263

AN XY:

74440

show subpopulations

African (AFR)

AF:

0.000770

AC:

AN:

41564

American (AMR)

AF:

0.00242

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.0138

AC:

146

AN:

10600

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00322

AC:

219

AN:

68020

Other (OTH)

AF:

0.00189

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

103

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00282

Hom.:

Bravo

AF:

0.00209

TwinsUK

AF:

0.00297

AC:

ALSPAC

AF:

0.00234

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00407

AC:

ExAC

AF:

0.00287

AC:

349

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00327

EpiControl

AF:

0.00344

ClinVar

ClinVar submissions as Germline

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Hirschsprung disease, susceptibility to, 1 (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.48

CADD

Benign

8.5

(source)

DANN

Benign

0.87

DEOGEN2

Benign

0.11

Eigen

Benign

-0.99

Eigen_PC

Benign

-0.94

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.36

MetaRNN

Benign

0.0052

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.97

PhyloP100

-0.093

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.17

REVEL

Benign

0.044

Sift

Benign

0.14

Sift4G

Benign

0.12

Polyphen

0.025

Vest4

0.22

MVP

0.082

MPC

0.17

ClinPred

0.0020

GERP RS

3.3

Varity_R

0.13

gMVP

0.43

Mutation Taster

=98/2

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over