chr9-104102442-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PM4
The NM_006444.3(SMC2):c.889C>T(p.Arg297Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000275 in 1,455,864 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 (★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_006444.3 stop_gained
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/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SMC2 | NM_006444.3 | c.889C>T | p.Arg297Ter | stop_gained | 9/25 | ENST00000374793.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SMC2 | ENST00000374793.8 | c.889C>T | p.Arg297Ter | stop_gained | 9/25 | 1 | NM_006444.3 | P1 | |
SMC2 | ENST00000286398.11 | c.889C>T | p.Arg297Ter | stop_gained | 9/25 | 1 | P1 | ||
SMC2 | ENST00000374787.7 | c.889C>T | p.Arg297Ter | stop_gained | 9/25 | 2 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000407 AC: 1AN: 245892Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 132894
GnomAD4 exome AF: 0.00000275 AC: 4AN: 1455864Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 724054
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 11, 2023 | This sequence change creates a premature translational stop signal (p.Arg297*) in the SMC2 gene. It is expected to result in an absent or disrupted protein product. However, the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in SMC2 cause disease. This variant is present in population databases (rs761107909, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with SMC2-related conditions. ClinVar contains an entry for this variant (Variation ID: 1015975). 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