rs121909654

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2PP3_StrongPP5

The ENST00000261937.11(FLT4):​c.2632G>A​(p.Val878Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 34)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

FLT4
ENST00000261937.11 missense

Scores

10
8
1

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 7.90
Variant links:
Genes affected
FLT4 (HGNC:3767): (fms related receptor tyrosine kinase 4) This gene encodes a tyrosine kinase receptor for vascular endothelial growth factors C and D. The protein is thought to be involved in lymphangiogenesis and maintenance of the lymphatic endothelium. Mutations in this gene cause hereditary lymphedema type IA. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.951
PP5
Variant 5-180619680-C-T is Pathogenic according to our data. Variant chr5-180619680-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 16265.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-180619680-C-T is described in Lovd as [Likely_pathogenic]. Variant chr5-180619680-C-T is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
FLT4NM_182925.5 linkuse as main transcriptc.2632G>A p.Val878Met missense_variant 18/30 ENST00000261937.11 NP_891555.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
FLT4ENST00000261937.11 linkuse as main transcriptc.2632G>A p.Val878Met missense_variant 18/301 NM_182925.5 ENSP00000261937 P1P35916-2

Frequencies

GnomAD3 genomes
Cov.:
34
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1459966
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
726316
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
34

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Hereditary lymphedema type I Pathogenic:1
Pathogenic, no assertion criteria providedliterature onlyOMIMOct 01, 2006- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.96
BayesDel_addAF
Pathogenic
0.43
D
BayesDel_noAF
Pathogenic
0.38
CADD
Pathogenic
33
DANN
Uncertain
1.0
DEOGEN2
Pathogenic
0.82
D;.;D
Eigen
Uncertain
0.63
Eigen_PC
Uncertain
0.52
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Pathogenic
0.99
D;D;D
M_CAP
Pathogenic
0.68
D
MetaRNN
Pathogenic
0.95
D;D;D
MetaSVM
Pathogenic
0.82
D
MutationAssessor
Uncertain
2.1
M;M;.
MutationTaster
Benign
1.0
A;A;A
PrimateAI
Uncertain
0.78
T
PROVEAN
Uncertain
-2.6
D;D;D
REVEL
Pathogenic
0.87
Sift
Uncertain
0.0010
D;D;D
Sift4G
Uncertain
0.0020
D;D;D
Polyphen
1.0
D;.;D
Vest4
0.86
MutPred
0.82
Gain of disorder (P = 0.0792);Gain of disorder (P = 0.0792);Gain of disorder (P = 0.0792);
MVP
0.91
MPC
1.6
ClinPred
0.99
D
GERP RS
4.3
Varity_R
0.73
gMVP
0.91

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs121909654; hg19: chr5-180046680; API