4-55111633-A-G

Variant names:

• chr4-55111633-A-G
• rs2034965
• NM_002253.4:c.977-865T>C

Variant summary

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

The NM_002253.4(KDR):​c.977-865T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.686 in 152,170 control chromosomes in the GnomAD database, including 36,355 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 0.69 (36355 hom., cov: 33)
• Consequence: KDR NM_002253.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.68
• Publications: 16 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 (EAS) allele frequency at 95% confidence interval = 0.78 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.977-865T>C		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.977-865T>C		intron	N/A	ENSP00000263923.4
	KDR	ENST00000512566.1	TSL:1	n.977-865T>C		intron	N/A
	KDR	ENST00000647068.1		n.990-865T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.685 AC: 104227 AN: 152052 Hom.: 36310 Cov.: 33

Gnomad AFR AF: 0.559

Gnomad AMI AF: 0.675

Gnomad AMR AF: 0.759

Gnomad ASJ AF: 0.602

Gnomad EAS AF: 0.800

Gnomad SAS AF: 0.571

Gnomad FIN AF: 0.730

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.743

Gnomad OTH AF: 0.697

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

GnomAD4 genome AF: 0.686 AC: 104332 AN: 152170 Hom.: 36355 Cov.: 33 AF XY: 0.687 AC XY: 51118 AN XY: 74404

African (AFR) AF: 0.559 AC: 23212 AN: 41492

American (AMR) AF: 0.759 AC: 11615 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.602 AC: 2088 AN: 3468

East Asian (EAS) AF: 0.800 AC: 4137 AN: 5172

South Asian (SAS) AF: 0.572 AC: 2759 AN: 4822

European-Finnish (FIN) AF: 0.730 AC: 7727 AN: 10584

Middle Eastern (MID) AF: 0.629 AC: 185 AN: 294

European-Non Finnish (NFE) AF: 0.743 AC: 50524 AN: 68018

Other (OTH) AF: 0.696 AC: 1471 AN: 2114

Alfa AF: 0.716 Hom.: 19453

Bravo AF: 0.683

Asia WGS AF: 0.699 AC: 2430 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	0.12
DANN	Benign	0.54
PhyloP100		-3.7
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: rs2034965; hg19: chr4-55977800;