rs201215425
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6BP7
The NM_014244.5(ADAMTS2):c.2817C>T(p.Ser939=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000183 in 1,612,846 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.00018 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00018 ( 0 hom. )
Consequence
ADAMTS2
NM_014244.5 synonymous
NM_014244.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -4.30
Genes affected
ADAMTS2 (HGNC:218): (ADAM metallopeptidase with thrombospondin type 1 motif 2) This gene encodes a member of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) protein family. Members of the family share several distinct protein modules, including a propeptide region, a metalloproteinase domain, a disintegrin-like domain, and a thrombospondin type 1 (TS) motif. Individual members of this family differ in the number of C-terminal TS motifs, and some have unique C-terminal domains. The encoded preproprotein is proteolytically processed to generate the mature procollagen N-proteinase. This proteinase excises the N-propeptide of the fibrillar procollagens types I-III and type V. Mutations in this gene cause Ehlers-Danlos syndrome type VIIC, a recessively inherited connective-tissue disorder. Alternative splicing results in multiple transcript variants, at least one of which encodes an isoform that is proteolytically processed. [provided by RefSeq, Feb 2016]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.76).
BP6
?
Variant 5-179125114-G-A is Benign according to our data. Variant chr5-179125114-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 353096.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=2, Likely_benign=2}.
BP7
?
Synonymous conserved (PhyloP=-4.3 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ADAMTS2 | NM_014244.5 | c.2817C>T | p.Ser939= | synonymous_variant | 19/22 | ENST00000251582.12 | |
ADAMTS2 | XM_047417895.1 | c.2322C>T | p.Ser774= | synonymous_variant | 18/21 | ||
ADAMTS2 | XM_047417896.1 | c.1935C>T | p.Ser645= | synonymous_variant | 17/20 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ADAMTS2 | ENST00000251582.12 | c.2817C>T | p.Ser939= | synonymous_variant | 19/22 | 1 | NM_014244.5 | P2 | |
ADAMTS2 | ENST00000518335.3 | c.2817C>T | p.Ser939= | synonymous_variant | 19/21 | 3 | A2 | ||
ADAMTS2 | ENST00000698889.1 | c.2817C>T | p.Ser939= | synonymous_variant, NMD_transcript_variant | 19/21 |
Frequencies
GnomAD3 genomes ? AF: 0.000184 AC: 28AN: 152180Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000156 AC: 39AN: 250416Hom.: 0 AF XY: 0.000148 AC XY: 20AN XY: 135508
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GnomAD4 exome AF: 0.000183 AC: 267AN: 1460666Hom.: 0 Cov.: 38 AF XY: 0.000165 AC XY: 120AN XY: 726690
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GnomAD4 genome ? AF: 0.000184 AC: 28AN: 152180Hom.: 0 Cov.: 33 AF XY: 0.000175 AC XY: 13AN XY: 74346
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:2Benign:3
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Ehlers-Danlos syndrome, dermatosparaxis type Uncertain:1Benign:2
Likely benign, no assertion criteria provided | clinical testing | Natera, Inc. | Feb 27, 2020 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 14, 2024 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Ehlers-Danlos syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Jul 11, 2022 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 17, 2020 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
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Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at