chr2-9526212-G-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_003183.6(ADAM17):c.652C>A(p.Pro218Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000161 in 1,613,296 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. P218P) has been classified as Likely benign.
Frequency
Consequence
NM_003183.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ADAM17 | NM_003183.6 | c.652C>A | p.Pro218Thr | missense_variant | 6/19 | ENST00000310823.8 | |
ADAM17 | XM_047445610.1 | c.559C>A | p.Pro187Thr | missense_variant | 7/20 | ||
ADAM17 | NM_001382777.1 | c.-9C>A | 5_prime_UTR_variant | 6/19 | |||
ADAM17 | NM_001382778.1 | c.-251C>A | 5_prime_UTR_variant | 6/19 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ADAM17 | ENST00000310823.8 | c.652C>A | p.Pro218Thr | missense_variant | 6/19 | 1 | NM_003183.6 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000132 AC: 2AN: 151978Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251070Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135698
GnomAD4 exome AF: 0.0000164 AC: 24AN: 1461318Hom.: 0 Cov.: 31 AF XY: 0.0000206 AC XY: 15AN XY: 726972
GnomAD4 genome AF: 0.0000132 AC: 2AN: 151978Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74220
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 13, 2021 | The c.652C>A (p.P218T) alteration is located in exon 6 (coding exon 6) of the ADAM17 gene. This alteration results from a C to A substitution at nucleotide position 652, causing the proline (P) at amino acid position 218 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Inflammatory skin and bowel disease, neonatal, 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 10, 2024 | This sequence change replaces proline, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 218 of the ADAM17 protein (p.Pro218Thr). This variant is present in population databases (rs373192089, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with ADAM17-related conditions. ClinVar contains an entry for this variant (Variation ID: 573989). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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