chr10-103089674-A-ATTC
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP3
The NM_001351169.2(NT5C2):c.1681_1683dupGAA(p.Glu561dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000066 in 151,556 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Consequence
NT5C2
NM_001351169.2 conservative_inframe_insertion
NM_001351169.2 conservative_inframe_insertion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -0.635
Genes affected
NT5C2 (HGNC:8022): (5'-nucleotidase, cytosolic II) This gene encodes a hydrolase that serves as an important role in cellular purine metabolism by acting primarily on inosine 5'-monophosphate and other purine nucleotides. [provided by RefSeq, Oct 2011]
CNNM2 (HGNC:103): (cyclin and CBS domain divalent metal cation transport mediator 2) This gene encodes a member of the ancient conserved domain containing protein family. Members of this protein family contain a cyclin box motif and have structural similarity to the cyclins. The encoded protein may play an important role in magnesium homeostasis by mediating the epithelial transport and renal reabsorption of Mg2+. Mutations in this gene are associated with renal hypomagnesemia. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2011]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP3
Nonframeshift variant in repetitive region in NM_001351169.2
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| NT5C2 | NM_001351169.2 | c.1681_1683dupGAA | p.Glu561dup | conservative_inframe_insertion | Exon 19 of 19 | ENST00000404739.8 | NP_001338098.1 | |
| CNNM2 | NM_017649.5 | c.*12498_*12500dupTTC | 3_prime_UTR_variant | Exon 8 of 8 | ENST00000369878.9 | NP_060119.3 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| NT5C2 | ENST00000404739.8 | c.1681_1683dupGAA | p.Glu561dup | conservative_inframe_insertion | Exon 19 of 19 | 1 | NM_001351169.2 | ENSP00000383960.3 | ||
| CNNM2 | ENST00000369878.9 | c.*12498_*12500dupTTC | 3_prime_UTR_variant | Exon 8 of 8 | 1 | NM_017649.5 | ENSP00000358894.3 |
Frequencies
GnomAD3 genomes 0.00000660 AC: 1AN: 151556Hom.: 0 Cov.: 32
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GnomAD4 genome 0.00000660 AC: 1AN: 151556Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 73956
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Hereditary spastic paraplegia 45 Uncertain:1
| Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jul 29, 2022 | Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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. This variant has not been reported in the literature in individuals affected with NT5C2-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.01%). This sequence change disrupts the translational stop signal of the NT5C2 mRNA. It is expected to extend the length of the NT5C2 protein by 1 additional amino acid residues. - |
Computational scores
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at