chr14-75634903-T-G
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_017791.3(FLVCR2):c.1021-7T>G variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000374 in 1,604,718 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_017791.3 splice_region, splice_polypyrimidine_tract, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
FLVCR2 | NM_017791.3 | c.1021-7T>G | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000238667.9 | NP_060261.2 | |||
FLVCR2 | NM_001195283.2 | c.406-7T>G | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | NP_001182212.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
FLVCR2 | ENST00000238667.9 | c.1021-7T>G | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_017791.3 | ENSP00000238667 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152182Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000400 AC: 1AN: 250100Hom.: 0 AF XY: 0.00000740 AC XY: 1AN XY: 135092
GnomAD4 exome AF: 0.00000275 AC: 4AN: 1452536Hom.: 0 Cov.: 29 AF XY: 0.00000277 AC XY: 2AN XY: 723232
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152182Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74360
ClinVar
Submissions by phenotype
Fowler syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Faculty of Engineering and Natural Sciences, Biruni University | Apr 20, 2023 | The c.1021-7T>G variant in the FLVCR2 (NM_017791.3) gene is a splicing region variant and computational prediction tools unanimously support a deleterious effect on the gene(PP3). To our knowledge, no experimental evidence has been reported showing an effect of this change on protein function. In the gnomAD database showing the population frequency, the frequency of this variant is reported to be very low, 0.000003998(PM2). As mentioned in the previous publication (PMID: 19635601), severe seizures with hydrocephalus were observed in the common ultrasound findings of the patient. Using exome sequencing, Lalonde et al. (2010) identified compound heterozygosity for 2 mutations in the FLVCR2 gene (610865.0006 and 610865.0007). It is thought that the c.191del variant, which was detected together with the c.1021-7T>G variant in the case, causes Fowler syndrome by causing compund heterozygote. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at