rs121909654
Positions:
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
ENST00000261937.11 missense
Scores
10
8
1
Clinical Significance
Conservation
PhyloP100: 7.90
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]
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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 |
---|---|---|---|---|---|---|---|---|
FLT4 | NM_182925.5 | c.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 |
---|---|---|---|---|---|---|---|---|---|---|
FLT4 | ENST00000261937.11 | c.2632G>A | p.Val878Met | missense_variant | 18/30 | 1 | NM_182925.5 | ENSP00000261937 | P1 |
Frequencies
GnomAD3 genomes Cov.: 34
GnomAD3 genomes
Cov.:
34
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1459966Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 726316
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1459966
Hom.:
Cov.:
32
AF XY:
AC XY:
0
AN XY:
726316
Gnomad4 AFR exome
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GnomAD4 genome Cov.: 34
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 provided | literature only | OMIM | Oct 01, 2006 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Pathogenic
D;.;D
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;D;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D
MetaSVM
Pathogenic
D
MutationAssessor
Uncertain
M;M;.
MutationTaster
Benign
A;A;A
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D
REVEL
Pathogenic
Sift
Uncertain
D;D;D
Sift4G
Uncertain
D;D;D
Polyphen
D;.;D
Vest4
MutPred
Gain of disorder (P = 0.0792);Gain of disorder (P = 0.0792);Gain of disorder (P = 0.0792);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at