rs758041605
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Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7
The NM_014244.5(ADAMTS2):c.1254C>T(p.His418=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000122 in 1,560,612 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 Likely benign (★).
Frequency
Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000099 ( 0 hom. )
Consequence
ADAMTS2
NM_014244.5 synonymous
NM_014244.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -3.35
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 -5 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.75).
BP6
?
Variant 5-179154177-G-A is Benign according to our data. Variant chr5-179154177-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 469661.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=-3.35 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ADAMTS2 | NM_014244.5 | c.1254C>T | p.His418= | synonymous_variant | 8/22 | ENST00000251582.12 | |
ADAMTS2 | NM_021599.4 | c.1254C>T | p.His418= | synonymous_variant | 8/11 | ||
ADAMTS2 | XM_047417895.1 | c.759C>T | p.His253= | synonymous_variant | 7/21 | ||
ADAMTS2 | XM_047417896.1 | c.372C>T | p.His124= | synonymous_variant | 6/20 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ADAMTS2 | ENST00000251582.12 | c.1254C>T | p.His418= | synonymous_variant | 8/22 | 1 | NM_014244.5 | P2 | |
ADAMTS2 | ENST00000274609.5 | c.1254C>T | p.His418= | synonymous_variant | 8/11 | 1 | |||
ADAMTS2 | ENST00000518335.3 | c.1254C>T | p.His418= | synonymous_variant | 8/21 | 3 | A2 | ||
ADAMTS2 | ENST00000698889.1 | c.1254C>T | p.His418= | synonymous_variant, NMD_transcript_variant | 8/21 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152162Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000184 AC: 3AN: 163308Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 88478
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GnomAD4 exome AF: 0.00000994 AC: 14AN: 1408450Hom.: 0 Cov.: 32 AF XY: 0.0000100 AC XY: 7AN XY: 697216
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GnomAD4 genome ? AF: 0.0000329 AC: 5AN: 152162Hom.: 0 Cov.: 33 AF XY: 0.0000404 AC XY: 3AN XY: 74328
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Ehlers-Danlos syndrome, dermatosparaxis type Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 21, 2023 | - - |
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