rs2034965

Positions:

• chr4-55111633-A-G
• chr4-55111633-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002253.4(KDR):​c.977-865T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.686 in 152,170 control chromosomes in the GnomAD database, including 36,355 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.69 (36355 hom., cov: 33)
• Consequence: KDR NM_002253.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.68

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.78 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KDR	NM_002253.4	c.977-865T>C		intron_variant		ENST00000263923.5	NP_002244.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KDR	ENST00000263923.5	c.977-865T>C		intron_variant		1	NM_002253.4	ENSP00000263923.4
KDR	ENST00000512566.1	n.977-865T>C		intron_variant		1
KDR	ENST00000647068.1	n.990-865T>C		intron_variant

Frequencies

GnomAD3 genomes AF: 0.685 AC: 104227 AN: 152052 Hom.: 36310 Cov.: 33

Gnomad AFR AF: 0.559

Gnomad AMI AF: 0.675

Gnomad AMR AF: 0.759

Gnomad ASJ AF: 0.602

Gnomad EAS AF: 0.800

Gnomad SAS AF: 0.571

Gnomad FIN AF: 0.730

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.743

Gnomad OTH AF: 0.697

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.686 AC: 104332 AN: 152170 Hom.: 36355 Cov.: 33 AF XY: 0.687 AC XY: 51118 AN XY: 74404

Gnomad4 AFR AF: 0.559

Gnomad4 AMR AF: 0.759

Gnomad4 ASJ AF: 0.602

Gnomad4 EAS AF: 0.800

Gnomad4 SAS AF: 0.572

Gnomad4 FIN AF: 0.730

Gnomad4 NFE AF: 0.743

Gnomad4 OTH AF: 0.696

Alfa AF: 0.717 Hom.: 16528

Bravo AF: 0.683

Asia WGS AF: 0.699 AC: 2430 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.12
DANN	Benign	0.54

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

LitVar

Other links and lift over

dbSNP: rs2034965; hg19: chr4-55977800;