2-9490236-C-A
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBS1_Supporting
The NM_003183.6(ADAM17):c.2416G>T(p.Ala806Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000087 in 1,609,752 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_003183.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ADAM17 | NM_003183.6 | c.2416G>T | p.Ala806Ser | missense_variant | 19/19 | ENST00000310823.8 | NP_003174.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ADAM17 | ENST00000310823.8 | c.2416G>T | p.Ala806Ser | missense_variant | 19/19 | 1 | NM_003183.6 | ENSP00000309968.3 |
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152248Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000517 AC: 13AN: 251398Hom.: 0 AF XY: 0.0000810 AC XY: 11AN XY: 135870
GnomAD4 exome AF: 0.0000919 AC: 134AN: 1457504Hom.: 0 Cov.: 31 AF XY: 0.0000994 AC XY: 72AN XY: 724038
GnomAD4 genome AF: 0.0000394 AC: 6AN: 152248Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74386
ClinVar
Submissions by phenotype
Inflammatory skin and bowel disease, neonatal, 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 15, 2021 | This sequence change replaces alanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 806 of the ADAM17 protein (p.Ala806Ser). This variant is present in population databases (rs761391373, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with ADAM17-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available"). 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