rs116708837
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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):c.1695C>T(p.Gly565=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000796 in 1,613,954 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0042 ( 4 hom., cov: 33)
Exomes 𝑓: 0.00044 ( 7 hom. )
Consequence
ADAMTS2
NM_014244.5 synonymous
NM_014244.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -4.79
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=-0.71).
BP6
?
Variant 5-179139970-G-A is Benign according to our data. Variant chr5-179139970-G-A is described in ClinVar as [Benign]. Clinvar id is 469665.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-4.79 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00418 (637/152290) while in subpopulation AFR AF= 0.0144 (598/41556). AF 95% confidence interval is 0.0134. There are 4 homozygotes in gnomad4. There are 286 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 4 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ADAMTS2 | NM_014244.5 | c.1695C>T | p.Gly565= | synonymous_variant | 11/22 | ENST00000251582.12 | |
ADAMTS2 | XM_047417895.1 | c.1200C>T | p.Gly400= | synonymous_variant | 10/21 | ||
ADAMTS2 | XM_047417896.1 | c.813C>T | p.Gly271= | synonymous_variant | 9/20 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ADAMTS2 | ENST00000251582.12 | c.1695C>T | p.Gly565= | synonymous_variant | 11/22 | 1 | NM_014244.5 | P2 | |
ADAMTS2 | ENST00000518335.3 | c.1695C>T | p.Gly565= | synonymous_variant | 11/21 | 3 | A2 | ||
ADAMTS2 | ENST00000698889.1 | c.1695C>T | p.Gly565= | synonymous_variant, NMD_transcript_variant | 11/21 |
Frequencies
GnomAD3 genomes ? AF: 0.00419 AC: 637AN: 152172Hom.: 4 Cov.: 33
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GnomAD3 exomes AF: 0.00112 AC: 281AN: 251406Hom.: 1 AF XY: 0.000743 AC XY: 101AN XY: 135886
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GnomAD4 exome AF: 0.000443 AC: 648AN: 1461664Hom.: 7 Cov.: 31 AF XY: 0.000377 AC XY: 274AN XY: 727140
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GnomAD4 genome ? AF: 0.00418 AC: 637AN: 152290Hom.: 4 Cov.: 33 AF XY: 0.00384 AC XY: 286AN XY: 74472
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ClinVar
Significance: Benign
Submissions summary: Benign:4
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 | 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 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. - |
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | Dec 02, 2019 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 25, 2024 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 26, 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