chr14-75579223-G-A
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PS1_ModeratePM2PP3_Moderate
The NM_017791.3(FLVCR2):c.251G>A(p.Arg84His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely pathogenicin UniProt.
Frequency
Consequence
NM_017791.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FLVCR2 | NM_017791.3 | c.251G>A | p.Arg84His | missense_variant | 1/10 | ENST00000238667.9 | |
FLVCR2-AS1 | NR_110552.1 | n.366C>T | non_coding_transcript_exon_variant | 1/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FLVCR2 | ENST00000238667.9 | c.251G>A | p.Arg84His | missense_variant | 1/10 | 1 | NM_017791.3 | P1 | |
FLVCR2-AS1 | ENST00000455232.1 | n.366C>T | non_coding_transcript_exon_variant | 1/3 | 1 | ||||
FLVCR2-AS1 | ENST00000693551.1 | n.430C>T | non_coding_transcript_exon_variant | 1/1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461894Hom.: 0 Cov.: 37 AF XY: 0.00 AC XY: 0AN XY: 727248
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 13, 2022 | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 84 of the FLVCR2 protein (p.Arg84His). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of FLVCR2-related conditions (PMID: 20690116). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at