chr5-179345227-G-GGGC
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP3BP6
The NM_014244.5(ADAMTS2):c.101_102insGCC(p.Pro33dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000515 in 1,119,552 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. P34P) has been classified as Likely benign.
Frequency
Consequence
NM_014244.5 inframe_insertion
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 |
---|---|---|---|---|---|---|---|
ADAMTS2 | NM_014244.5 | c.101_102insGCC | p.Pro33dup | inframe_insertion | 1/22 | ENST00000251582.12 | |
ADAMTS2 | NM_021599.4 | c.101_102insGCC | p.Pro33dup | inframe_insertion | 1/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ADAMTS2 | ENST00000251582.12 | c.101_102insGCC | p.Pro33dup | inframe_insertion | 1/22 | 1 | NM_014244.5 | P2 | |
ADAMTS2 | ENST00000274609.5 | c.101_102insGCC | p.Pro33dup | inframe_insertion | 1/11 | 1 | |||
ADAMTS2 | ENST00000518335.3 | c.101_102insGCC | p.Pro33dup | inframe_insertion | 1/21 | 3 | A2 | ||
ADAMTS2 | ENST00000698889.1 | c.101_102insGCC | p.Pro33dup | inframe_insertion, NMD_transcript_variant | 1/21 |
Frequencies
GnomAD3 genomes ? AF: 0.000229 AC: 34AN: 148190Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.000559 AC: 543AN: 971260Hom.: 0 Cov.: 29 AF XY: 0.000518 AC XY: 240AN XY: 463420
GnomAD4 genome ? AF: 0.000229 AC: 34AN: 148292Hom.: 0 Cov.: 32 AF XY: 0.000180 AC XY: 13AN XY: 72288
ClinVar
Submissions by phenotype
Ehlers-Danlos syndrome, dermatosparaxis type Uncertain:1Other:1
not provided, no classification provided | phenotyping only | GenomeConnect - Invitae Patient Insights Network | - | Variant interpreted as Uncertain significance and reported on 12-14-2020 by Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 26, 2022 | This variant, c.99_101dup, results in the insertion of 1 amino acid(s) of the ADAMTS2 protein (p.Pro34dup), but otherwise preserves the integrity of the reading frame. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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: 509635). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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. - |
Ehlers-Danlos syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Mar 14, 2022 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 05, 2020 | In-frame duplication of 1 amino acids in a repetitive region with no known function; In silico analysis 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