chr4-55110690-G-T

Variant names:

• chr4-55110690-G-T
• rs151317075
• NM_002253.4:c.1055C>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_002253.4(KDR):​c.1055C>A​(p.Ala352Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A352V) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: KDR NM_002253.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.90
• Publications: 0 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KDR	NM_002253.4	c.1055C>A	p.Ala352Glu	missense_variant	Exon 8 of 30	ENST00000263923.5	NP_002244.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KDR	ENST00000263923.5	c.1055C>A	p.Ala352Glu	missense_variant	Exon 8 of 30	1	NM_002253.4	ENSP00000263923.4
KDR	ENST00000512566.1	n.1055C>A		non_coding_transcript_exon_variant	Exon 8 of 13	1
KDR	ENST00000647068.1	n.1068C>A		non_coding_transcript_exon_variant	Exon 8 of 30

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.53
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.20	T;T
Eigen	Benign	-0.056
Eigen_PC	Benign	0.0046
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.59	.;T
M_CAP	Uncertain	0.24	D
MetaRNN	Uncertain	0.73	D;D
MetaSVM	Benign	-0.41	T
MutationAssessor	Uncertain	2.3	M;M
PhyloP100		4.9
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-1.8	.;N
REVEL	Uncertain	0.49
Sift	Uncertain	0.0010	.;D
Sift4G	Uncertain	0.0080	.;D
Polyphen		0.46	P;P
Vest4		0.64
MutPred		0.73		Gain of disorder (P = 0.0598);Gain of disorder (P = 0.0598);
MVP		0.40
MPC		0.33
ClinPred		0.96	D
GERP RS		4.5
Varity_R		0.83
gMVP		0.92
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

dbSNP: rs151317075; hg19: chr4-55976857;