4-55097934-T-C

Variant names:

• chr4-55097934-T-C
• rs6838752
• NM_002253.4:c.2510-168A>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.2510-168A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 151,286 control chromosomes in the GnomAD database, including 3,761 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

• Frequency: Genomes: 𝑓 0.21 (3761 hom., cov: 31)
• Consequence: KDR NM_002253.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.731
• 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.441 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.2510-168A>G		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.2510-168A>G		intron	N/A	ENSP00000263923.4	P35968-1
	KDR	ENST00000922964.1		c.2168-168A>G		intron	N/A	ENSP00000593023.1
	KDR	ENST00000647068.1		n.2523-168A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.209 AC: 31662 AN: 151168 Hom.: 3755 Cov.: 31

Gnomad AFR AF: 0.118

Gnomad AMI AF: 0.395

Gnomad AMR AF: 0.149

Gnomad ASJ AF: 0.205

Gnomad EAS AF: 0.456

Gnomad SAS AF: 0.172

Gnomad FIN AF: 0.313

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.245

Gnomad OTH AF: 0.203

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

GnomAD4 genome AF: 0.209 AC: 31678 AN: 151286 Hom.: 3761 Cov.: 31 AF XY: 0.212 AC XY: 15647 AN XY: 73838

African (AFR) AF: 0.118 AC: 4851 AN: 41260

American (AMR) AF: 0.148 AC: 2244 AN: 15122

Ashkenazi Jewish (ASJ) AF: 0.205 AC: 710 AN: 3466

East Asian (EAS) AF: 0.456 AC: 2341 AN: 5132

South Asian (SAS) AF: 0.172 AC: 820 AN: 4770

European-Finnish (FIN) AF: 0.313 AC: 3263 AN: 10422

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.245 AC: 16600 AN: 67826

Other (OTH) AF: 0.209 AC: 435 AN: 2086

Alfa AF: 0.225 Hom.: 6759

Bravo AF: 0.193

Asia WGS AF: 0.311 AC: 1083 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.4
DANN	Benign	0.49
PhyloP100		0.73
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: rs6838752; hg19: chr4-55964101;