rs370350117
Variant summary
Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4
The NM_014244.5(ADAMTS2):c.2414C>T(p.Thr805Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000446 in 1,614,048 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 (★★). Synonymous variant affecting the same amino acid position (i.e. T805T) has been classified as Likely benign.
Frequency
Consequence
NM_014244.5 missense
Scores
Clinical Significance
Conservation
Publications
- Ehlers-Danlos syndrome, dermatosparaxis typeInheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Orphanet, G2P, PanelApp Australia, Illumina
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ACMG classification
Our verdict: Uncertain_significance. The variant received 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ADAMTS2 | NM_014244.5 | c.2414C>T | p.Thr805Met | missense_variant | Exon 16 of 22 | ENST00000251582.12 | NP_055059.2 | |
ADAMTS2 | XM_047417895.1 | c.1919C>T | p.Thr640Met | missense_variant | Exon 15 of 21 | XP_047273851.1 | ||
ADAMTS2 | XM_047417896.1 | c.1532C>T | p.Thr511Met | missense_variant | Exon 14 of 20 | XP_047273852.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ADAMTS2 | ENST00000251582.12 | c.2414C>T | p.Thr805Met | missense_variant | Exon 16 of 22 | 1 | NM_014244.5 | ENSP00000251582.7 | ||
ADAMTS2 | ENST00000518335.3 | c.2414C>T | p.Thr805Met | missense_variant | Exon 16 of 21 | 3 | ENSP00000489888.2 | |||
ADAMTS2 | ENST00000698889.1 | n.2414C>T | non_coding_transcript_exon_variant | Exon 16 of 21 | ENSP00000514008.1 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152198Hom.: 0 Cov.: 32 show subpopulations
GnomAD2 exomes AF: 0.0000438 AC: 11AN: 251102 AF XY: 0.0000294 show subpopulations
GnomAD4 exome AF: 0.0000479 AC: 70AN: 1461732Hom.: 0 Cov.: 32 AF XY: 0.0000454 AC XY: 33AN XY: 727178 show subpopulations
Age Distribution
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152316Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74486 show subpopulations
Age Distribution
ClinVar
Submissions by phenotype
Ehlers-Danlos syndrome, dermatosparaxis type Uncertain:2
This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 805 of the ADAMTS2 protein (p.Thr805Met). This variant is present in population databases (rs370350117, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with ADAMTS2-related conditions. ClinVar contains an entry for this variant (Variation ID: 537396). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. 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. -
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not provided Uncertain:1
Has not been previously published as pathogenic or benign to our knowledge; Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at