rs17085310

chr4-55104615-G-Achr4-55104615-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002253.4(KDR):c.1987+28C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0112 in 1,580,432 control chromosomes in the GnomAD database, including 709 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

• Frequency:
  • Genomes: 𝑓 0.014 (73 hom., cov: 32)
  • Exomes 𝑓: 0.011 (636 hom.)
• Consequence: KDR NM_002253.4 intron
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: -0.658

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0789 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KDR	NM_002253.4	c.1987+28C>T		intron_variant		ENST00000263923.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KDR	ENST00000263923.5	c.1987+28C>T		intron_variant		1	NM_002253.4	P1
KDR	ENST00000512566.1	n.2015C>T		non_coding_transcript_exon_variant	13/13	1
KDR	ENST00000647068.1	n.2000+28C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0136 AC: 2072 AN: 152128 Hom.: 73 Cov.: 32

Gnomad AFR AF: 0.00179

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0574

Gnomad ASJ AF: 0.00288

Gnomad EAS AF: 0.0853

Gnomad SAS AF: 0.0457

Gnomad FIN AF: 0.0197

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00318

Gnomad OTH AF: 0.0115

GnomAD3 exomes AF: 0.0303 AC: 7393 AN: 244128 Hom.: 366 AF XY: 0.0262 AC XY: 3458 AN XY: 132090

Gnomad AFR exome AF: 0.00175

Gnomad AMR exome AF: 0.115

Gnomad ASJ exome AF: 0.00181

Gnomad EAS exome AF: 0.0870

Gnomad SAS exome AF: 0.0317

Gnomad FIN exome AF: 0.0184

Gnomad NFE exome AF: 0.00396

Gnomad OTH exome AF: 0.0186

GnomAD4 exome AF: 0.0110 AC: 15678 AN: 1428186 Hom.: 636 Cov.: 28 AF XY: 0.0109 AC XY: 7780 AN XY: 712138

Gnomad4 AFR exome AF: 0.00113

Gnomad4 AMR exome AF: 0.108

Gnomad4 ASJ exome AF: 0.00190

Gnomad4 EAS exome AF: 0.0956

Gnomad4 SAS exome AF: 0.0308

Gnomad4 FIN exome AF: 0.0197

Gnomad4 NFE exome AF: 0.00235

Gnomad4 OTH exome AF: 0.0140

GnomAD4 genome AF: 0.0136 AC: 2069 AN: 152246 Hom.: 73 Cov.: 32 AF XY: 0.0154 AC XY: 1149 AN XY: 74418

Gnomad4 AFR AF: 0.00178

Gnomad4 AMR AF: 0.0572

Gnomad4 ASJ AF: 0.00288

Gnomad4 EAS AF: 0.0855

Gnomad4 SAS AF: 0.0452

Gnomad4 FIN AF: 0.0197

Gnomad4 NFE AF: 0.00318

Gnomad4 OTH AF: 0.0118

Alfa AF: 0.0143 Hom.: 21

Bravo AF: 0.0175

Asia WGS AF: 0.0700 AC: 242 AN: 3478

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

Submissions by phenotype

not specified Other:1

not provided, no classification provided

reference population

ITMI

Sep 19, 2013

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	0.23
Dann	Benign	0.41

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

Publications

LitVar

Other links and lift over

dbSNP: rs17085310; hg19: chr4-55970782; COSMIC: COSV55758709;