rs770913783
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong
The NM_001303256.3(MORC2):c.1370-3C>T 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 0.00000991 in 1,613,924 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 predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_001303256.3 splice_region, splice_polypyrimidine_tract, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MORC2 | NM_001303256.3 | c.1370-3C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000397641.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MORC2 | ENST00000397641.8 | c.1370-3C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 5 | NM_001303256.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 152048Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251380Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135854
GnomAD4 exome AF: 0.0000103 AC: 15AN: 1461876Hom.: 0 Cov.: 34 AF XY: 0.00000963 AC XY: 7AN XY: 727236
GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 152048Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74278
ClinVar
Submissions by phenotype
Charcot-Marie-Tooth disease axonal type 2Z Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 15, 2023 | 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. 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 is not likely to affect RNA splicing. ClinVar contains an entry for this variant (Variation ID: 577793). This variant has not been reported in the literature in individuals affected with MORC2-related conditions. This variant is present in population databases (rs770913783, gnomAD 0.002%). This sequence change falls in intron 14 of the MORC2 gene. It does not directly change the encoded amino acid sequence of the MORC2 protein. It affects a nucleotide within the consensus splice site. - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 13, 2021 | The c.1370-3C>T intronic variant results from a C to T substitution 3 nucleotides upstream from coding exon 15 in the MORC2 gene. This nucleotide position is not well conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will not have any significant effect on splicing. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at