rs587777769
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Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_001368809.2(AMPD2):c.157del(p.Cys53AlafsTer80) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,622 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
AMPD2
NM_001368809.2 frameshift
NM_001368809.2 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 1.20
Genes affected
AMPD2 (HGNC:469): (adenosine monophosphate deaminase 2) The protein encoded by this gene is important in purine metabolism by converting AMP to IMP. The encoded protein, which acts as a homotetramer, is one of three AMP deaminases found in mammals. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2012]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 11 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 1-109625367-CT-C is Pathogenic according to our data. Variant chr1-109625367-CT-C is described in ClinVar as [Pathogenic]. Clinvar id is 101075.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr1-109625367-CT-C is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
AMPD2 | NM_001368809.2 | c.157del | p.Cys53AlafsTer80 | frameshift_variant | 3/19 | ENST00000528667.7 | NP_001355738.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
AMPD2 | ENST00000528667.7 | c.157del | p.Cys53AlafsTer80 | frameshift_variant | 3/19 | 1 | NM_001368809.2 | ENSP00000436541 | P1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461622Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 727148
GnomAD4 exome
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32
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727148
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GnomAD4 genome Cov.: 33
GnomAD4 genome
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33
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Hereditary spastic paraplegia 63 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jan 31, 2014 | - - |
Computational scores
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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