NM_002253.4:c.977-441G>A

Variant names:

• chr4-55111209-C-T
• rs17085326
• NM_002253.4:c.977-441G>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.977-441G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0834 in 152,178 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 0.083 (574 hom., cov: 32)
• Consequence: KDR NM_002253.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.93
• Publications: 5 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0895 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KDR	NM_002253.4	MANE Select	c.977-441G>A		intron	N/A	NP_002244.1	P35968-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KDR	ENST00000263923.5	TSL:1 MANE Select	c.977-441G>A		intron	N/A	ENSP00000263923.4	P35968-1
	KDR	ENST00000512566.1	TSL:1	n.977-441G>A		intron	N/A
	KDR	ENST00000922964.1		c.977-441G>A		intron	N/A	ENSP00000593023.1

Frequencies

GnomAD3 genomes AF: 0.0834 AC: 12686 AN: 152060 Hom.: 575 Cov.: 32

Gnomad AFR AF: 0.0918

Gnomad AMI AF: 0.0329

Gnomad AMR AF: 0.0628

Gnomad ASJ AF: 0.109

Gnomad EAS AF: 0.00772

Gnomad SAS AF: 0.0334

Gnomad FIN AF: 0.130

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0843

Gnomad OTH AF: 0.0815

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

GnomAD4 genome AF: 0.0834 AC: 12695 AN: 152178 Hom.: 574 Cov.: 32 AF XY: 0.0845 AC XY: 6288 AN XY: 74400

African (AFR) AF: 0.0919 AC: 3815 AN: 41512

American (AMR) AF: 0.0627 AC: 959 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.109 AC: 376 AN: 3464

East Asian (EAS) AF: 0.00773 AC: 40 AN: 5172

South Asian (SAS) AF: 0.0334 AC: 161 AN: 4822

European-Finnish (FIN) AF: 0.130 AC: 1381 AN: 10602

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.0843 AC: 5735 AN: 67996

Other (OTH) AF: 0.0802 AC: 169 AN: 2108

Alfa AF: 0.0830 Hom.: 369

Bravo AF: 0.0800

Asia WGS AF: 0.0270 AC: 95 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.60
DANN	Benign	0.50
PhyloP100		-1.9
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: rs17085326; hg19: chr4-55977376;