NM_002253.4:c.1987+709T>G

Variant names:

• chr4-55103934-A-C
• rs11732292
• NM_002253.4:c.1987+709T>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.1987+709T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.351 in 151,964 control chromosomes in the GnomAD database, including 9,490 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 (9490 hom., cov: 32)
• Consequence: KDR NM_002253.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.13
• Publications: 8 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.465 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002253.4. 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.1987+709T>G		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.1987+709T>G		intron	N/A	ENSP00000263923.4
	KDR	ENST00000647068.1		n.2000+709T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.351 AC: 53285 AN: 151846 Hom.: 9466 Cov.: 32

Gnomad AFR AF: 0.313

Gnomad AMI AF: 0.380

Gnomad AMR AF: 0.473

Gnomad ASJ AF: 0.319

Gnomad EAS AF: 0.307

Gnomad SAS AF: 0.306

Gnomad FIN AF: 0.368

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.352

Gnomad OTH AF: 0.347

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

GnomAD4 genome AF: 0.351 AC: 53346 AN: 151964 Hom.: 9490 Cov.: 32 AF XY: 0.354 AC XY: 26291 AN XY: 74266

African (AFR) AF: 0.313 AC: 12957 AN: 41446

American (AMR) AF: 0.474 AC: 7237 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.319 AC: 1106 AN: 3468

East Asian (EAS) AF: 0.307 AC: 1580 AN: 5146

South Asian (SAS) AF: 0.308 AC: 1481 AN: 4812

European-Finnish (FIN) AF: 0.368 AC: 3892 AN: 10562

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

European-Non Finnish (NFE) AF: 0.352 AC: 23948 AN: 67944

Other (OTH) AF: 0.343 AC: 726 AN: 2116

Alfa AF: 0.346 Hom.: 35009

Bravo AF: 0.360

Asia WGS AF: 0.286 AC: 992 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.17
DANN	Benign	0.45
PhyloP100		-1.1
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: rs11732292; hg19: chr4-55970101;