18-47841846-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 5P and 2B. PM1PM2PP2BP4_Moderate
The NM_005901.6(SMAD2):c.1385G>A(p.Arg462His) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,190 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R462C) has been classified as Uncertain significance.
Frequency
Consequence
NM_005901.6 missense
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 |
---|---|---|---|---|---|---|---|
SMAD2 | NM_005901.6 | c.1385G>A | p.Arg462His | missense_variant | 11/11 | ENST00000262160.11 | |
SMAD2 | NM_001003652.4 | c.1385G>A | p.Arg462His | missense_variant | 11/11 | ||
SMAD2 | NM_001135937.3 | c.1295G>A | p.Arg432His | missense_variant | 10/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SMAD2 | ENST00000262160.11 | c.1385G>A | p.Arg462His | missense_variant | 11/11 | 1 | NM_005901.6 | ||
SMAD2 | ENST00000402690.6 | c.1385G>A | p.Arg462His | missense_variant | 11/11 | 1 | |||
SMAD2 | ENST00000356825.8 | c.1295G>A | p.Arg432His | missense_variant | 10/10 | 1 | P1 | ||
SMAD2 | ENST00000586040.5 | c.1295G>A | p.Arg432His | missense_variant | 9/9 | 5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152190Hom.: 0 Cov.: 32
GnomAD4 exome Cov.: 31
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152190Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74346
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Aug 15, 2019 | Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at