NM_002253.4:c.798+54G>A

Variant names:

• chr4-55114072-C-T
• rs7692791
• NM_002253.4:c.798+54G>A

Variant summary

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

The NM_002253.4(KDR):​c.798+54G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.541 in 1,606,028 control chromosomes in the GnomAD database, including 238,033 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 0.51 (19834 hom., cov: 32)
  • Exomes 𝑓: 0.54 (218199 hom.)
• Consequence: KDR NM_002253.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.304
• Publications: 46 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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.662 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.798+54G>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.798+54G>A		intron	N/A	ENSP00000263923.4
	KDR	ENST00000512566.1	TSL:1	n.798+54G>A		intron	N/A
	KDR	ENST00000647068.1		n.811+54G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.507 AC: 76946 AN: 151882 Hom.: 19832 Cov.: 32

Gnomad AFR AF: 0.418

Gnomad AMI AF: 0.622

Gnomad AMR AF: 0.444

Gnomad ASJ AF: 0.673

Gnomad EAS AF: 0.631

Gnomad SAS AF: 0.683

Gnomad FIN AF: 0.550

Gnomad MID AF: 0.668

Gnomad NFE AF: 0.534

Gnomad OTH AF: 0.525

GnomAD4 exome AF: 0.545 AC: 791865 AN: 1454026 Hom.: 218199 AF XY: 0.550 AC XY: 398303 AN XY: 723802

African (AFR) AF: 0.410 AC: 13636 AN: 33294

American (AMR) AF: 0.399 AC: 17839 AN: 44690

Ashkenazi Jewish (ASJ) AF: 0.684 AC: 17827 AN: 26062

East Asian (EAS) AF: 0.640 AC: 25365 AN: 39630

South Asian (SAS) AF: 0.681 AC: 58627 AN: 86090

European-Finnish (FIN) AF: 0.549 AC: 29278 AN: 53330

Middle Eastern (MID) AF: 0.632 AC: 3631 AN: 5742

European-Non Finnish (NFE) AF: 0.536 AC: 592208 AN: 1105038

Other (OTH) AF: 0.556 AC: 33454 AN: 60150

GnomAD4 genome AF: 0.506 AC: 76976 AN: 152002 Hom.: 19834 Cov.: 32 AF XY: 0.506 AC XY: 37573 AN XY: 74262

African (AFR) AF: 0.418 AC: 17333 AN: 41426

American (AMR) AF: 0.443 AC: 6770 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.673 AC: 2334 AN: 3470

East Asian (EAS) AF: 0.631 AC: 3258 AN: 5160

South Asian (SAS) AF: 0.682 AC: 3284 AN: 4818

European-Finnish (FIN) AF: 0.550 AC: 5808 AN: 10564

Middle Eastern (MID) AF: 0.656 AC: 193 AN: 294

European-Non Finnish (NFE) AF: 0.534 AC: 36309 AN: 67976

Other (OTH) AF: 0.531 AC: 1120 AN: 2110

Alfa AF: 0.528 Hom.: 62813

Bravo AF: 0.493

Asia WGS AF: 0.666 AC: 2315 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.036
DANN	Benign	0.64
PhyloP100		-0.30
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: rs7692791; hg19: chr4-55980239; COSMIC: COSV55757809;