rs2168945

Positions:

• chr4-55101316-A-C
• chr4-55101316-A-G

Variant summary

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

The NM_002253.4(KDR):​c.2266+581T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.304 in 152,108 control chromosomes in the GnomAD database, including 7,791 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 0.30 (7791 hom., cov: 33)
• Consequence: KDR NM_002253.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.15

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.448 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KDR	NM_002253.4	c.2266+581T>G		intron_variant		ENST00000263923.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KDR	ENST00000263923.5	c.2266+581T>G		intron_variant		1	NM_002253.4	P1
KDR	ENST00000647068.1	n.2279+581T>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.304 AC: 46206 AN: 151988 Hom.: 7775 Cov.: 33

Gnomad AFR AF: 0.150

Gnomad AMI AF: 0.379

Gnomad AMR AF: 0.456

Gnomad ASJ AF: 0.316

Gnomad EAS AF: 0.310

Gnomad SAS AF: 0.309

Gnomad FIN AF: 0.367

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.352

Gnomad OTH AF: 0.313

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

GnomAD4 genome AF: 0.304 AC: 46239 AN: 152108 Hom.: 7791 Cov.: 33 AF XY: 0.307 AC XY: 22842 AN XY: 74354

Gnomad4 AFR AF: 0.149

Gnomad4 AMR AF: 0.457

Gnomad4 ASJ AF: 0.316

Gnomad4 EAS AF: 0.309

Gnomad4 SAS AF: 0.311

Gnomad4 FIN AF: 0.367

Gnomad4 NFE AF: 0.352

Gnomad4 OTH AF: 0.310

Alfa AF: 0.343 Hom.: 8403

Bravo AF: 0.307

Asia WGS AF: 0.271 AC: 942 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	8.0
DANN	Benign	0.77

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: rs2168945; hg19: chr4-55967483;