7-44062937-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_000290.4(PGAM2):c.596-7G>A 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 0.0000787 in 1,614,126 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign 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_000290.4 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 | UniProt |
---|---|---|---|---|---|---|---|
DBNL | NM_001014436.3 | c.*2021C>T | 3_prime_UTR_variant | 13/13 | ENST00000448521.6 | ||
PGAM2 | NM_000290.4 | c.596-7G>A | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000297283.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DBNL | ENST00000448521.6 | c.*2021C>T | 3_prime_UTR_variant | 13/13 | 1 | NM_001014436.3 | P4 | ||
PGAM2 | ENST00000297283.4 | c.596-7G>A | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_000290.4 | P1 | |||
DBNL | ENST00000432854.5 | c.*2021C>T | 3_prime_UTR_variant | 11/11 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000591 AC: 9AN: 152178Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000557 AC: 14AN: 251334Hom.: 0 AF XY: 0.0000662 AC XY: 9AN XY: 135856
GnomAD4 exome AF: 0.0000807 AC: 118AN: 1461830Hom.: 0 Cov.: 31 AF XY: 0.0000866 AC XY: 63AN XY: 727220
GnomAD4 genome ? AF: 0.0000591 AC: 9AN: 152296Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3AN XY: 74468
ClinVar
Submissions by phenotype
Glycogen storage disease type X Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Apr 05, 2023 | This sequence change falls in intron 2 of the PGAM2 gene. It does not directly change the encoded amino acid sequence of the PGAM2 protein. 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. ClinVar contains an entry for this variant (Variation ID: 1424881). This variant has not been reported in the literature in individuals affected with PGAM2-related conditions. This variant is present in population databases (rs372222997, gnomAD 0.009%). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at