rs2125489

Variant names:

• chr4-55087316-G-A
• rs2125489
• NM_002253.4:c.3662+291C>T

Your query was ambiguous. Multiple possible variants found:

• chr4-55087316-G-A
• chr4-55087316-G-C
• chr4-55087316-G-T

Variant summary

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

The NM_002253.4(KDR):​c.3662+291C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0757 in 152,264 control chromosomes in the GnomAD database, including 574 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 0.076 (574 hom., cov: 33)
• Consequence: KDR NM_002253.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.23
• Publications: 17 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

ENSG00000250646 (HGNC:58789):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KDR	NM_002253.4	c.3662+291C>T		intron_variant	Intron 27 of 29	ENST00000263923.5	NP_002244.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KDR	ENST00000263923.5	c.3662+291C>T		intron_variant	Intron 27 of 29	1	NM_002253.4	ENSP00000263923.4
ENSG00000250646	ENST00000511222.1	n.234-4997G>A		intron_variant	Intron 3 of 3	5
KDR	ENST00000647068.1	n.3675+291C>T		intron_variant	Intron 27 of 29

Frequencies

GnomAD3 genomes AF: 0.0758 AC: 11540 AN: 152146 Hom.: 575 Cov.: 33

Gnomad AFR AF: 0.0207

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.0754

Gnomad ASJ AF: 0.0582

Gnomad EAS AF: 0.0227

Gnomad SAS AF: 0.0839

Gnomad FIN AF: 0.112

Gnomad MID AF: 0.0605

Gnomad NFE AF: 0.109

Gnomad OTH AF: 0.0909

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

GnomAD4 genome AF: 0.0757 AC: 11533 AN: 152264 Hom.: 574 Cov.: 33 AF XY: 0.0748 AC XY: 5566 AN XY: 74434

African (AFR) AF: 0.0206 AC: 856 AN: 41560

American (AMR) AF: 0.0752 AC: 1151 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0582 AC: 202 AN: 3468

East Asian (EAS) AF: 0.0226 AC: 117 AN: 5184

South Asian (SAS) AF: 0.0834 AC: 402 AN: 4822

European-Finnish (FIN) AF: 0.112 AC: 1186 AN: 10598

Middle Eastern (MID) AF: 0.0616 AC: 18 AN: 292

European-Non Finnish (NFE) AF: 0.109 AC: 7397 AN: 68018

Other (OTH) AF: 0.0904 AC: 191 AN: 2112

Alfa AF: 0.0912 Hom.: 1564

Bravo AF: 0.0710

Asia WGS AF: 0.0530 AC: 183 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	17
DANN	Benign	0.73
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: rs2125489; hg19: chr4-55953483;