5-74722378-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PVS1_ModeratePM2
The NM_032380.5(GFM2):c.2211+1G>A variant causes a splice donor, intron change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000137 in 1,459,954 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_032380.5 splice_donor, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
GFM2 | NM_032380.5 | c.2211+1G>A | splice_donor_variant, intron_variant | Intron 20 of 20 | ENST00000296805.8 | NP_115756.2 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.0000200 AC: 5AN: 250360Hom.: 0 AF XY: 0.0000296 AC XY: 4AN XY: 135334
GnomAD4 exome AF: 0.0000137 AC: 20AN: 1459954Hom.: 0 Cov.: 30 AF XY: 0.0000193 AC XY: 14AN XY: 726374
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not provided Uncertain:1
This sequence change falls in intron 20 of the GFM2 gene. It does not directly change the encoded amino acid sequence of the GFM2 protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs749490366, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with GFM2-related conditions. ClinVar contains an entry for this variant (Variation ID: 1440709). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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