4-55110507-G-T

Variant names:

• chr4-55110507-G-T
• NM_002253.4:c.1151C>A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_002253.4(KDR):​c.1151C>A​(p.Thr384Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000123 in 1,461,704 control chromosomes in the GnomAD database, with no homozygous occurrence. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: KDR NM_002253.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.80

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]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 18 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KDR	NM_002253.4	c.1151C>A	p.Thr384Lys	missense_variant	Exon 9 of 30	ENST00000263923.5	NP_002244.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KDR	ENST00000263923.5	c.1151C>A	p.Thr384Lys	missense_variant	Exon 9 of 30	1	NM_002253.4	ENSP00000263923.4
KDR	ENST00000512566.1	n.1151C>A		non_coding_transcript_exon_variant	Exon 9 of 13	1
KDR	ENST00000647068.1	n.1164C>A		non_coding_transcript_exon_variant	Exon 9 of 30

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000123 AC: 18 AN: 1461704 Hom.: 0 Cov.: 33 AF XY: 0.0000138 AC XY: 10 AN XY: 727174

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: 0.0000153

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Uncertain	0.099	D
BayesDel_noAF	Benign	-0.10
CADD	Benign	17
DANN	Benign	0.97
DEOGEN2	Benign	0.15	T;T
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.14
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.69	.;T
M_CAP	Benign	0.067	D
MetaRNN	Uncertain	0.57	D;D
MetaSVM	Benign	-0.55	T
MutationAssessor	Benign	1.5	L;L
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.8	.;N
REVEL	Uncertain	0.42
Sift	Uncertain	0.022	.;D
Sift4G	Benign	0.064	.;T
Polyphen		0.77	P;P
Vest4		0.44
MutPred		0.73		Gain of ubiquitination at T384 (P = 0.017);Gain of ubiquitination at T384 (P = 0.017);
MVP		0.55
MPC		0.48
ClinPred		0.69	D
GERP RS		4.8
Varity_R		0.31
gMVP		0.76

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-55976674;