chr4-55101316-A-C

Variant names:

• chr4-55101316-A-C
• rs2168945
• NM_002253.4:c.2266+581T>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 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=-0.83).
• 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 rank	MANE	Protein	UniProt
KDR	NM_002253.4	c.2266+581T>G		intron_variant	Intron 15 of 29	ENST00000263923.5	NP_002244.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KDR	ENST00000263923.5	c.2266+581T>G		intron_variant	Intron 15 of 29	1	NM_002253.4	ENSP00000263923.4
KDR	ENST00000647068.1	n.2279+581T>G		intron_variant	Intron 15 of 29

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

African (AFR) AF: 0.149 AC: 6205 AN: 41514

American (AMR) AF: 0.457 AC: 6981 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.316 AC: 1096 AN: 3470

East Asian (EAS) AF: 0.309 AC: 1601 AN: 5176

South Asian (SAS) AF: 0.311 AC: 1497 AN: 4820

European-Finnish (FIN) AF: 0.367 AC: 3883 AN: 10568

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.352 AC: 23906 AN: 67980

Other (OTH) AF: 0.310 AC: 654 AN: 2112

Alfa AF: 0.340 Hom.: 11194

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
PhyloP100		1.2
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: rs2168945; hg19: chr4-55967483;