rs587777769

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

Scores

Not classified

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 1.20
Variant links:
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
AMPD2NM_001368809.2 linkuse as main transcriptc.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
AMPD2ENST00000528667.7 linkuse as main transcriptc.157del p.Cys53AlafsTer80 frameshift_variant 3/191 NM_001368809.2 ENSP00000436541 P1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461622
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
727148
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
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 providedliterature onlyOMIMJan 31, 2014- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs587777769; hg19: chr1-110167989; API