chr14-75579022-C-CG
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1_StrongPM2PP5_Moderate
The NM_017791.3(FLVCR2):c.52dup(p.Glu18GlyfsTer52) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. P17P) has been classified as Likely benign.
Frequency
Genomes: not found (cov: 32)
Consequence
FLVCR2
NM_017791.3 frameshift
NM_017791.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -0.698
Genes affected
FLVCR2 (HGNC:20105): (FLVCR choline and putative heme transporter 2) This gene encodes a member of the major facilitator superfamily. The encoded transmembrane protein is a calcium transporter. Unlike the related protein feline leukemia virus subgroup C receptor 1, the protein encoded by this locus does not bind to feline leukemia virus subgroup C envelope protein. The encoded protein may play a role in development of brain vascular endothelial cells, as mutations at this locus have been associated with proliferative vasculopathy and hydranencephaly-hydrocephaly syndrome. Alternatively spliced transcript variants have been described.[provided by RefSeq, Aug 2010]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
PVS1
?
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 18 pathogenic variants in the truncated region.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 14-75579022-C-CG is Pathogenic according to our data. Variant chr14-75579022-C-CG is described in ClinVar as [Pathogenic]. Clinvar id is 3011058.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FLVCR2 | NM_017791.3 | c.52dup | p.Glu18GlyfsTer52 | frameshift_variant | 1/10 | ENST00000238667.9 | |
FLVCR2-AS1 | NR_110552.1 | n.566_567insC | non_coding_transcript_exon_variant | 1/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FLVCR2 | ENST00000238667.9 | c.52dup | p.Glu18GlyfsTer52 | frameshift_variant | 1/10 | 1 | NM_017791.3 | P1 | |
FLVCR2-AS1 | ENST00000455232.1 | n.566_567insC | non_coding_transcript_exon_variant | 1/3 | 1 | ||||
FLVCR2-AS1 | ENST00000693551.1 | n.630_631insC | non_coding_transcript_exon_variant | 1/1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 37
GnomAD4 exome
Cov.:
37
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Sep 14, 2023 | This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Glu18Glyfs*52) in the FLVCR2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in FLVCR2 are known to be pathogenic (PMID: 20206334, 20690116). This variant has not been reported in the literature in individuals affected with FLVCR2-related conditions. For these reasons, this variant has been classified as Pathogenic. - |
Computational scores
Source:
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Calibrated prediction
Score
Prediction
Splicing
Name
Calibrated prediction
Score
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.