rs528367185
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_014244.5(ADAMTS2):āc.935A>Gā(p.Asn312Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00015 in 1,614,018 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 Uncertain significance (ā ā ). Synonymous variant affecting the same amino acid position (i.e. N312N) has been classified as Benign.
Frequency
Consequence
NM_014244.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ADAMTS2 | NM_014244.5 | c.935A>G | p.Asn312Ser | missense_variant | 5/22 | ENST00000251582.12 | |
ADAMTS2 | NM_021599.4 | c.935A>G | p.Asn312Ser | missense_variant | 5/11 | ||
ADAMTS2 | XM_047417895.1 | c.440A>G | p.Asn147Ser | missense_variant | 4/21 | ||
ADAMTS2 | XM_047417896.1 | c.53A>G | p.Asn18Ser | missense_variant | 3/20 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ADAMTS2 | ENST00000251582.12 | c.935A>G | p.Asn312Ser | missense_variant | 5/22 | 1 | NM_014244.5 | P2 | |
ADAMTS2 | ENST00000274609.5 | c.935A>G | p.Asn312Ser | missense_variant | 5/11 | 1 | |||
ADAMTS2 | ENST00000518335.3 | c.935A>G | p.Asn312Ser | missense_variant | 5/21 | 3 | A2 | ||
ADAMTS2 | ENST00000698889.1 | c.935A>G | p.Asn312Ser | missense_variant, NMD_transcript_variant | 5/21 |
Frequencies
GnomAD3 genomes ? AF: 0.000177 AC: 27AN: 152116Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000171 AC: 43AN: 251344Hom.: 0 AF XY: 0.000162 AC XY: 22AN XY: 135896
GnomAD4 exome AF: 0.000147 AC: 215AN: 1461784Hom.: 0 Cov.: 31 AF XY: 0.000146 AC XY: 106AN XY: 727186
GnomAD4 genome ? AF: 0.000177 AC: 27AN: 152234Hom.: 0 Cov.: 32 AF XY: 0.000202 AC XY: 15AN XY: 74430
ClinVar
Submissions by phenotype
Ehlers-Danlos syndrome, dermatosparaxis type Uncertain:4
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 12, 2022 | This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 312 of the ADAMTS2 protein (p.Asn312Ser). This variant is present in population databases (rs528367185, gnomAD 0.08%). This variant has not been reported in the literature in individuals affected with ADAMTS2-related conditions. ClinVar contains an entry for this variant (Variation ID: 373235). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Dec 03, 2020 | - - |
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Jan 24, 2020 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Nov 29, 2021 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Nov 22, 2016 | The N312S variant in the ADAMTS2 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. This variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The N312S variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret N312S as a variant of uncertain significance. - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 05, 2022 | The c.935A>G (p.N312S) alteration is located in exon 5 (coding exon 5) of the ADAMTS2 gene. This alteration results from a A to G substitution at nucleotide position 935, causing the asparagine (N) at amino acid position 312 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Ehlers-Danlos syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Jul 13, 2022 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at