Genetic Variant NM_002253.4:c.3487C>T (chr4-55088891-G-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_002253.4(KDR):c.3487C>T(p.Leu1163Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,674 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

KDR
NM_002253.4 missense

Scores

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 3.02

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:

ENSG00000250646 (HGNC:):

ENSG00000250646 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3576879).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KDR	NM_002253.4 link	c.3487C>T	p.Leu1163Phe	missense_variant	Exon 26 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.3487C>T	p.Leu1163Phe	missense_variant	Exon 26 of 30	1	NM_002253.4	ENSP00000263923.4	P35968-1
KDR	ENST00000647068.1 link	n.3500C>T		non_coding_transcript_exon_variant	Exon 26 of 30
ENSG00000250646	ENST00000511222.1 link	n.234-3422G>A		intron_variant	Intron 3 of 3	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251284

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135816

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461674

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727164

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Carcinoma of colon

Uncertain:1

Jan 24, 2015

Immunobiology Lab; University of Kashmir

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: case-control

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.36

BayesDel_addAF

Pathogenic

0.20

BayesDel_noAF

Uncertain

0.050

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.54

D;D

Eigen

Benign

0.13

Eigen_PC

Benign

0.20

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.81

.;T

M_CAP

Uncertain

0.11

MetaRNN

Benign

0.36

T;T

MetaSVM

Uncertain

-0.18

MutationAssessor

Pathogenic

3.0

M;M

PrimateAI

Uncertain

0.71

PROVEAN

Uncertain

-3.6

.;D

REVEL

Uncertain

0.52

Sift

Uncertain

0.011

.;D

Sift4G

Uncertain

0.027

.;D

Polyphen

0.33

B;B

Vest4

0.73

MutPred

0.38

Gain of helix (P = 0.132);Gain of helix (P = 0.132);

MVP

0.63

MPC

0.093

ClinPred

0.93

GERP RS

4.3

Varity_R

0.77

gMVP

0.67

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