rs2305945

Variant names:

• chr4-55105679-G-T
• rs2305945
• NM_002253.4:c.1645+153C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000263923.5(KDR):​c.1645+153C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.35 in 152,032 control chromosomes in the GnomAD database, including 9,435 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 0.35 (9435 hom., cov: 32)
• Consequence: KDR ENST00000263923.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.479
• Publications: 10 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.464 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000263923.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KDR	NM_002253.4	MANE Select	c.1645+153C>A		intron	N/A	NP_002244.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KDR	ENST00000263923.5	TSL:1 MANE Select	c.1645+153C>A		intron	N/A	ENSP00000263923.4
	KDR	ENST00000512566.1	TSL:1	n.1645+153C>A		intron	N/A
	KDR	ENST00000647068.1		n.1658+153C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.350 AC: 53173 AN: 151912 Hom.: 9411 Cov.: 32

Gnomad AFR AF: 0.312

Gnomad AMI AF: 0.379

Gnomad AMR AF: 0.472

Gnomad ASJ AF: 0.319

Gnomad EAS AF: 0.306

Gnomad SAS AF: 0.307

Gnomad FIN AF: 0.367

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.351

Gnomad OTH AF: 0.346

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

GnomAD4 genome AF: 0.350 AC: 53233 AN: 152032 Hom.: 9435 Cov.: 32 AF XY: 0.353 AC XY: 26236 AN XY: 74304

African (AFR) AF: 0.312 AC: 12922 AN: 41454

American (AMR) AF: 0.473 AC: 7229 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.319 AC: 1107 AN: 3472

East Asian (EAS) AF: 0.306 AC: 1578 AN: 5162

South Asian (SAS) AF: 0.309 AC: 1485 AN: 4812

European-Finnish (FIN) AF: 0.367 AC: 3884 AN: 10572

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.351 AC: 23888 AN: 67964

Other (OTH) AF: 0.342 AC: 721 AN: 2108

Alfa AF: 0.343 Hom.: 2083

Bravo AF: 0.359

Asia WGS AF: 0.285 AC: 991 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.7
DANN	Benign	0.25
PhyloP100		0.48
Mutation Taster		=100/0	polymorphism (auto)

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: rs2305945; hg19: chr4-55971846;