rs587778426

Variant names:

• chr4-55096283-T-C
• rs587778426
• NM_002253.4:c.2674A>G

Your query was ambiguous. Multiple possible variants found:

• chr4-55096283-T-C
• chr4-55096283-T-G

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_002253.4(KDR):​c.2674A>G​(p.Ile892Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as not provided (no stars). Synonymous variant affecting the same amino acid position (i.e. I892I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: KDR NM_002253.4 missense
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 8.02
• Publications: 1 publications found

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.798

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KDR	NM_002253.4	c.2674A>G	p.Ile892Val	missense_variant	Exon 19 of 30	ENST00000263923.5	NP_002244.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KDR	ENST00000263923.5	c.2674A>G	p.Ile892Val	missense_variant	Exon 19 of 30	1	NM_002253.4	ENSP00000263923.4
KDR	ENST00000509309.1	n.438A>G		non_coding_transcript_exon_variant	Exon 1 of 3	3
KDR	ENST00000647068.1	n.2687A>G		non_coding_transcript_exon_variant	Exon 19 of 30

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

Submissions by phenotype

not specified Other:1

Sep 19, 2013

ITMI

Significance: not provided

Review Status: no classification provided

Collection Method: reference population

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.47
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.040
CADD	Uncertain	26
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.26	T;T
Eigen	Uncertain	0.61
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.87	.;D
M_CAP	Uncertain	0.20	D
MetaRNN	Pathogenic	0.80	D;D
MetaSVM	Uncertain	0.54	D
MutationAssessor	Benign	0.16	N;N
PhyloP100		8.0
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-0.88	.;N
REVEL	Uncertain	0.61
Sift	Pathogenic	0.0	.;D
Sift4G	Pathogenic	0.0	.;D
Polyphen		1.0	D;D
Vest4		0.46
MutPred		0.68		Loss of catalytic residue at I892 (P = 0.0788);Loss of catalytic residue at I892 (P = 0.0788);
MVP		0.36
MPC		0.62
ClinPred		0.88	D
GERP RS		6.1
Varity_R		0.89
gMVP		0.54
Mutation Taster		=59/41	polymorphism

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

Other links and lift over

dbSNP: rs587778426; hg19: chr4-55962450;