rs73806887
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_014244.5(ADAMTS2):āc.3279T>Cā(p.Cys1093Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00134 in 1,613,802 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: š 0.0070 ( 12 hom., cov: 32)
Exomes š: 0.00075 ( 14 hom. )
Consequence
ADAMTS2
NM_014244.5 synonymous
NM_014244.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.208
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 Benign. Variant got -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.77).
BP6
Variant 5-179114224-A-G is Benign according to our data. Variant chr5-179114224-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 517917.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-179114224-A-G is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=0.208 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00698 (1063/152298) while in subpopulation AFR AF= 0.0242 (1006/41556). AF 95% confidence interval is 0.023. There are 12 homozygotes in gnomad4. There are 529 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 12 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ADAMTS2 | NM_014244.5 | c.3279T>C | p.Cys1093Cys | synonymous_variant | 22/22 | ENST00000251582.12 | NP_055059.2 | |
ADAMTS2 | XM_047417895.1 | c.2784T>C | p.Cys928Cys | synonymous_variant | 21/21 | XP_047273851.1 | ||
ADAMTS2 | XM_047417896.1 | c.2397T>C | p.Cys799Cys | synonymous_variant | 20/20 | XP_047273852.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ADAMTS2 | ENST00000251582.12 | c.3279T>C | p.Cys1093Cys | synonymous_variant | 22/22 | 1 | NM_014244.5 | ENSP00000251582.7 | ||
ADAMTS2 | ENST00000522937.1 | n.295T>C | non_coding_transcript_exon_variant | 2/2 | 2 |
Frequencies
GnomAD3 genomes AF: 0.00696 AC: 1059AN: 152180Hom.: 12 Cov.: 32
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GnomAD3 exomes AF: 0.00192 AC: 482AN: 251224Hom.: 6 AF XY: 0.00136 AC XY: 184AN XY: 135756
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GnomAD4 exome AF: 0.000752 AC: 1099AN: 1461504Hom.: 14 Cov.: 32 AF XY: 0.000637 AC XY: 463AN XY: 726964
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GnomAD4 genome AF: 0.00698 AC: 1063AN: 152298Hom.: 12 Cov.: 32 AF XY: 0.00710 AC XY: 529AN XY: 74478
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Ehlers-Danlos syndrome, dermatosparaxis type Benign:3
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 31, 2024 | - - |
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | Dec 02, 2019 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Ehlers-Danlos syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Nov 29, 2021 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 13, 2019 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at