chr18-47841942-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PP2PP3
The NM_005901.6(SMAD2):c.1289C>T(p.Thr430Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000062 in 1,613,946 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 (★). Synonymous variant affecting the same amino acid position (i.e. T430T) has been classified as Likely benign.
Frequency
Consequence
NM_005901.6 missense
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 |
---|---|---|---|---|---|---|---|
SMAD2 | NM_005901.6 | c.1289C>T | p.Thr430Met | missense_variant | 11/11 | ENST00000262160.11 | |
SMAD2 | NM_001003652.4 | c.1289C>T | p.Thr430Met | missense_variant | 11/11 | ||
SMAD2 | NM_001135937.3 | c.1199C>T | p.Thr400Met | missense_variant | 10/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SMAD2 | ENST00000262160.11 | c.1289C>T | p.Thr430Met | missense_variant | 11/11 | 1 | NM_005901.6 | ||
SMAD2 | ENST00000402690.6 | c.1289C>T | p.Thr430Met | missense_variant | 11/11 | 1 | |||
SMAD2 | ENST00000356825.8 | c.1199C>T | p.Thr400Met | missense_variant | 10/10 | 1 | P1 | ||
SMAD2 | ENST00000586040.5 | c.1199C>T | p.Thr400Met | missense_variant | 9/9 | 5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152192Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000400 AC: 1AN: 250234Hom.: 0 AF XY: 0.00000739 AC XY: 1AN XY: 135392
GnomAD4 exome AF: 0.00000616 AC: 9AN: 1461754Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 727176
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152192Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74350
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 22, 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt SMAD2 protein function. This variant has not been reported in the literature in individuals affected with SMAD2-related conditions. This variant is present in population databases (rs747308534, gnomAD 0.01%). This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 430 of the SMAD2 protein (p.Thr430Met). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at