rs151317075

Positions:

• chr4-55110690-G-A
• chr4-55110690-G-C
• chr4-55110690-G-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_002253.4(KDR):​c.1055C>T​(p.Ala352Val) variant causes a missense change. The variant allele was found at a frequency of 0.000285 in 1,613,304 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0014 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00017 (2 hom.)
• Consequence: KDR NM_002253.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1 O:1
• Conservation: PhyloP100: 4.90

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.009578437).
• BP6: Variant 4-55110690-G-A is Benign according to our data. Variant chr4-55110690-G-A is described in ClinVar as [Benign]. Clinvar id is 134617.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 208 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KDR	NM_002253.4	c.1055C>T	p.Ala352Val	missense_variant	8/30	ENST00000263923.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KDR	ENST00000263923.5	c.1055C>T	p.Ala352Val	missense_variant	8/30	1	NM_002253.4	P1
KDR	ENST00000512566.1	n.1055C>T		non_coding_transcript_exon_variant	8/13	1
KDR	ENST00000647068.1	n.1068C>T		non_coding_transcript_exon_variant	8/30

Frequencies

GnomAD3 genomes AF: 0.00138 AC: 209 AN: 151416 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00486

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000394

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.000482

GnomAD3 exomes AF: 0.000386 AC: 97 AN: 251298 Hom.: 1 AF XY: 0.000331 AC XY: 45 AN XY: 135856

Gnomad AFR exome AF: 0.00500

Gnomad AMR exome AF: 0.000231

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000980

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.000489

GnomAD4 exome AF: 0.000172 AC: 251 AN: 1461772 Hom.: 2 Cov.: 33 AF XY: 0.000150 AC XY: 109 AN XY: 727200

Gnomad4 AFR exome AF: 0.00520

Gnomad4 AMR exome AF: 0.000358

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0000928

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000279

Gnomad4 OTH exome AF: 0.000265

GnomAD4 genome AF: 0.00137 AC: 208 AN: 151532 Hom.: 0 Cov.: 32 AF XY: 0.00135 AC XY: 100 AN XY: 73984

Gnomad4 AFR AF: 0.00482

Gnomad4 AMR AF: 0.000394

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.000477

Alfa AF: 0.000271 Hom.: 1

Bravo AF: 0.00165

ESP6500AA AF: 0.00500 AC: 22

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000527 AC: 64

ClinVar

Significance: Benign

Submissions summary: Benign:1 Other:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 31, 2018

- -

not specified Other:1

not provided, no classification provided

reference population

ITMI

Sep 19, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.050
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	17
DANN	Benign	0.15
DEOGEN2	Benign	0.070	T;T
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.51
FATHMM_MKL	Benign	0.033	N
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.0096	T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-0.86	N;N
MutationTaster	Benign	1.0	N
PrimateAI	Uncertain	0.57	T
Polyphen		0.0	B;B
Vest4		0.35
MVP		0.10
MPC		0.16
ClinPred		0.0090	T
GERP RS		4.5
Varity_R		0.16
gMVP		0.62

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: rs151317075; hg19: chr4-55976857; COSMIC: COSV55758966;