chr4-55102578-C-T

Variant names:

• chr4-55102578-C-T
• rs13135562
• NM_002253.4:c.1988-70G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002253.4(KDR):​c.1988-70G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000717 in 1,393,844 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 33)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: KDR NM_002253.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.307
• Publications: 0 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: 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=-0.83).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KDR	NM_002253.4	c.1988-70G>A		intron_variant	Intron 13 of 29	ENST00000263923.5	NP_002244.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KDR	ENST00000263923.5	c.1988-70G>A		intron_variant	Intron 13 of 29	1	NM_002253.4	ENSP00000263923.4
KDR	ENST00000647068.1	n.2001-70G>A		intron_variant	Intron 13 of 29

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.17e-7 AC: 1 AN: 1393844 Hom.: 0 AF XY: 0.00000144 AC XY: 1 AN XY: 696596

African (AFR) AF: 0.00 AC: 0 AN: 32080

American (AMR) AF: 0.00 AC: 0 AN: 43962

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25644

East Asian (EAS) AF: 0.00 AC: 0 AN: 39154

South Asian (SAS) AF: 0.00 AC: 0 AN: 84430

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51820

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5636

European-Non Finnish (NFE) AF: 9.50e-7 AC: 1 AN: 1053028

Other (OTH) AF: 0.00 AC: 0 AN: 58090

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.9
DANN	Benign	0.50
PhyloP100		-0.31

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: rs13135562; hg19: chr4-55968745;