rs113121239

Positions:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_002253.4(KDR):c.1116G>C(p.Glu372Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00133 in 1,613,908 control chromosomes in the GnomAD database, including 30 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0073 ( 16 hom., cov: 32)

Exomes 𝑓: 0.00070 ( 14 hom. )

Consequence

KDR
NM_002253.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2O:1

Conservation

PhyloP100: 0.0870

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008658975).

BP6

Variant 4-55110542-C-G is Benign according to our data. Variant chr4-55110542-C-G is described in ClinVar as [Benign]. Clinvar id is 134619.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00735 (1118/152152) while in subpopulation AFR AF= 0.0258 (1073/41512). AF 95% confidence interval is 0.0246. There are 16 homozygotes in gnomad4. There are 547 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1118 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KDR	NM_002253.4 linkuse as main transcript	c.1116G>C	p.Glu372Asp	missense_variant	9/30	ENST00000263923.5	NP_002244.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KDR	ENST00000263923.5 linkuse as main transcript	c.1116G>C	p.Glu372Asp	missense_variant	9/30	1	NM_002253.4	ENSP00000263923	P1	P35968-1
KDR	ENST00000512566.1 linkuse as main transcript	n.1116G>C		non_coding_transcript_exon_variant	9/13	1
KDR	ENST00000647068.1 linkuse as main transcript	n.1129G>C		non_coding_transcript_exon_variant	9/30

Frequencies

GnomAD3 genomes

AF:

0.00732

AC:

1113

AN:

152034

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0258

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00203

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00383

GnomAD3 exomes

AF:

0.00184

AC:

463

AN:

251298

Hom.:

AF XY:

0.00139

AC XY:

189

AN XY:

135806

show subpopulations

Gnomad AFR exome

AF:

0.0245

Gnomad AMR exome

AF:

0.00159

Gnomad ASJ exome

AF:

0.000199

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000352

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000704

AC:

1029

AN:

1461756

Hom.:

Cov.:

AF XY:

0.000586

AC XY:

426

AN XY:

727170

show subpopulations

Gnomad4 AFR exome

AF:

0.0247

Gnomad4 AMR exome

AF:

0.00159

Gnomad4 ASJ exome

AF:

0.000268

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000207

Gnomad4 OTH exome

AF:

0.00151

GnomAD4 genome

AF:

0.00735

AC:

1118

AN:

152152

Hom.:

Cov.:

AF XY:

0.00735

AC XY:

547

AN XY:

74392

show subpopulations

Gnomad4 AFR

AF:

0.0258

Gnomad4 AMR

AF:

0.00203

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00379

Alfa

AF:

0.000335

Hom.:

Bravo

AF:

0.00797

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.0191

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00244

AC:

296

Asia WGS

AF:

0.00318

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:2Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

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

0.088

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.11

T;T

Eigen

Benign

-0.37

Eigen_PC

Benign

-0.34

FATHMM_MKL

Benign

0.63

LIST_S2

Benign

0.59

.;T

MetaRNN

Benign

0.0087

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.46

N;N

MutationTaster

Benign

0.93

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.56

.;N

REVEL

Benign

0.12

Sift

Benign

0.32

.;T

Sift4G

Benign

0.44

.;T

Polyphen

0.51

P;P

Vest4

0.14

MutPred

0.36

Loss of disorder (P = 0.2161);Loss of disorder (P = 0.2161);

MVP

0.18

MPC

0.22

ClinPred

0.016

GERP RS

1.5

Varity_R

0.25

gMVP

0.56

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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