Genetic Variant KDR:c.1987+130C>A (chr4-55104513-G-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_002253.4(KDR):c.1987+130C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

KDR
NM_002253.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.851

Publications

13 publications found

Variant links:

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

KDR links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KDR	NM_002253.4 link	c.1987+130C>A		intron_variant	Intron 13 of 29	ENST00000263923.5	NP_002244.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
KDR	ENST00000263923.5 link	c.1987+130C>A	intron_variant	Intron 13 of 29	1	NM_002253.4	ENSP00000263923.4
KDR	ENST00000647068.1 link	n.2000+130C>A	intron_variant	Intron 13 of 29
KDR	ENST00000512566.1 link	n.*80C>A	downstream_gene_variant		1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

591182

Hom.:

AF XY:

0.00

AC XY:

AN XY:

314832

African (AFR)

AF:

0.00

AC:

AN:

16116

American (AMR)

AF:

0.00

AC:

AN:

31330

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19444

East Asian (EAS)

AF:

0.00

AC:

AN:

32098

South Asian (SAS)

AF:

0.00

AC:

AN:

59738

European-Finnish (FIN)

AF:

0.00

AC:

AN:

35488

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4048

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

361272

Other (OTH)

AF:

0.00

AC:

AN:

31648

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

3247

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.0070

(source)

DANN

Benign

0.51

PhyloP100

-0.85

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over