NM_002253.4:c.1987+130C>T

Variant names:

• chr4-55104513-G-A
• rs13109660
• NM_002253.4:c.1987+130C>T

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+130C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.337 in 742,436 control chromosomes in the GnomAD database, including 44,324 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 0.30 (7746 hom., cov: 32)
  • Exomes 𝑓: 0.35 (36578 hom.)
• Consequence: KDR NM_002253.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.851
• Publications: 13 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.448 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+130C>T		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+130C>T		intron	N/A	ENSP00000263923.4
	KDR	ENST00000647068.1		n.2000+130C>T		intron	N/A
	KDR	ENST00000512566.1	TSL:1	n.*80C>T		downstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.304 AC: 46077 AN: 151780 Hom.: 7729 Cov.: 32

Gnomad AFR AF: 0.149

Gnomad AMI AF: 0.380

Gnomad AMR AF: 0.456

Gnomad ASJ AF: 0.318

Gnomad EAS AF: 0.307

Gnomad SAS AF: 0.306

Gnomad FIN AF: 0.369

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.351

Gnomad OTH AF: 0.312

GnomAD4 exome AF: 0.346 AC: 204132 AN: 590536 Hom.: 36578 AF XY: 0.343 AC XY: 107958 AN XY: 314494

African (AFR) AF: 0.148 AC: 2376 AN: 16106

American (AMR) AF: 0.527 AC: 16488 AN: 31300

Ashkenazi Jewish (ASJ) AF: 0.318 AC: 6176 AN: 19416

East Asian (EAS) AF: 0.323 AC: 10379 AN: 32086

South Asian (SAS) AF: 0.318 AC: 18957 AN: 59690

European-Finnish (FIN) AF: 0.378 AC: 13409 AN: 35466

Middle Eastern (MID) AF: 0.253 AC: 1025 AN: 4044

European-Non Finnish (NFE) AF: 0.346 AC: 124974 AN: 360798

Other (OTH) AF: 0.327 AC: 10348 AN: 31630

GnomAD4 genome AF: 0.304 AC: 46112 AN: 151900 Hom.: 7746 Cov.: 32 AF XY: 0.307 AC XY: 22787 AN XY: 74220

African (AFR) AF: 0.149 AC: 6182 AN: 41414

American (AMR) AF: 0.457 AC: 6982 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.318 AC: 1104 AN: 3470

East Asian (EAS) AF: 0.307 AC: 1582 AN: 5156

South Asian (SAS) AF: 0.308 AC: 1477 AN: 4798

European-Finnish (FIN) AF: 0.369 AC: 3879 AN: 10522

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.351 AC: 23839 AN: 67944

Other (OTH) AF: 0.309 AC: 651 AN: 2110

Alfa AF: 0.320 Hom.: 3247

Bravo AF: 0.306

Asia WGS AF: 0.270 AC: 937 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.013
DANN	Benign	0.62
PhyloP100		-0.85
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: rs13109660; hg19: chr4-55970680; COSMIC: COSV55757296; COSMIC: COSV55757296;