5-179345228-GGCGGCGGCGGCGGCGGCAGGA-GGCGGCGGCGGCGGCGGCAGGAGCGGCGGCGGCGGCGGCAGGAGCGGCGGCGGCGGCGGCAGGA
Variant summary
Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP3
The NM_014244.5(ADAMTS2):c.100_101insTCCTGCCGCCGCCGCCGCCGCTCCTGCCGCCGCCGCCGCCGC(p.Pro33_Pro34insLeuLeuProProProProProLeuLeuProProProProPro) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000136 in 147,326 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. P34P) has been classified as Likely benign.
Frequency
Consequence
NM_014244.5 conservative_inframe_insertion
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: Likely_benign. The variant received -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ADAMTS2 | NM_014244.5 | c.100_101insTCCTGCCGCCGCCGCCGCCGCTCCTGCCGCCGCCGCCGCCGC | p.Pro33_Pro34insLeuLeuProProProProProLeuLeuProProProProPro | conservative_inframe_insertion | Exon 1 of 22 | ENST00000251582.12 | NP_055059.2 | |
ADAMTS2 | NM_021599.4 | c.100_101insTCCTGCCGCCGCCGCCGCCGCTCCTGCCGCCGCCGCCGCCGC | p.Pro33_Pro34insLeuLeuProProProProProLeuLeuProProProProPro | conservative_inframe_insertion | Exon 1 of 11 | NP_067610.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ADAMTS2 | ENST00000251582.12 | c.100_101insTCCTGCCGCCGCCGCCGCCGCTCCTGCCGCCGCCGCCGCCGC | p.Pro33_Pro34insLeuLeuProProProProProLeuLeuProProProProPro | conservative_inframe_insertion | Exon 1 of 22 | 1 | NM_014244.5 | ENSP00000251582.7 | ||
ADAMTS2 | ENST00000274609.5 | c.100_101insTCCTGCCGCCGCCGCCGCCGCTCCTGCCGCCGCCGCCGCCGC | p.Pro33_Pro34insLeuLeuProProProProProLeuLeuProProProProPro | conservative_inframe_insertion | Exon 1 of 11 | 1 | ENSP00000274609.5 | |||
ADAMTS2 | ENST00000518335.3 | c.100_101insTCCTGCCGCCGCCGCCGCCGCTCCTGCCGCCGCCGCCGCCGC | p.Pro33_Pro34insLeuLeuProProProProProLeuLeuProProProProPro | conservative_inframe_insertion | Exon 1 of 21 | 3 | ENSP00000489888.2 | |||
ADAMTS2 | ENST00000698889.1 | n.100_101insTCCTGCCGCCGCCGCCGCCGCTCCTGCCGCCGCCGCCGCCGC | non_coding_transcript_exon_variant | Exon 1 of 21 | ENSP00000514008.1 |
Frequencies
GnomAD3 genomes AF: 0.0000136 AC: 2AN: 147326Hom.: 0 Cov.: 33 show subpopulations
GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000107 AC: 1AN: 934818Hom.: 0 Cov.: 30 AF XY: 0.00000225 AC XY: 1AN XY: 445130 show subpopulations
GnomAD4 genome AF: 0.0000136 AC: 2AN: 147326Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 71752 show subpopulations
ClinVar
Submissions by phenotype
Ehlers-Danlos syndrome, dermatosparaxis type Uncertain:1
This variant, c.100_101insTCCTGCCGCCGCCGCCGCCGCTCCTGCCGCCGCCGCCGCCGC, results in the insertion of 14 amino acid(s) of the ADAMTS2 protein (p.Pro33_Pro34insLeuLeuProProProProProLeuLeuProProProProPro), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with ADAMTS2-related conditions. 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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at