chr11-74343332-C-A
Position:
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_173582.6(PGM2L1):c.1303G>T(p.Glu435Ter) variant causes a stop gained change. The variant allele was found at a frequency of 0.00000894 in 1,454,340 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000089 ( 0 hom. )
Consequence
PGM2L1
NM_173582.6 stop_gained
NM_173582.6 stop_gained
Scores
5
1
1
Clinical Significance
Conservation
PhyloP100: 5.86
Genes affected
PGM2L1 (HGNC:20898): (phosphoglucomutase 2 like 1) Enables glucose-1,6-bisphosphate synthase activity. Predicted to be involved in glucose metabolic process and phosphorylation. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 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 11-74343332-C-A is Pathogenic according to our data. Variant chr11-74343332-C-A is described in ClinVar as [Pathogenic]. Clinvar id is 2283908.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PGM2L1 | NM_173582.6 | c.1303G>T | p.Glu435Ter | stop_gained | 10/14 | ENST00000298198.5 | |
LOC112268078 | XR_002957258.2 | n.314+13844C>A | intron_variant, non_coding_transcript_variant | ||||
PGM2L1 | XM_011544953.4 | c.1366G>T | p.Glu456Ter | stop_gained | 11/15 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PGM2L1 | ENST00000298198.5 | c.1303G>T | p.Glu435Ter | stop_gained | 10/14 | 1 | NM_173582.6 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 0.00000894 AC: 13AN: 1454340Hom.: 0 Cov.: 32 AF XY: 0.0000111 AC XY: 8AN XY: 723524
GnomAD4 exome
AF:
AC:
13
AN:
1454340
Hom.:
Cov.:
32
AF XY:
AC XY:
8
AN XY:
723524
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Inborn genetic diseases Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Ambry Genetics | May 10, 2022 | The c.1303G>T (p.E435*) alteration, located in exon 10 (coding exon 10) of the PGM2L1 gene, consists of a G to T substitution at nucleotide position 1303. This changes the amino acid from a glutamic acid (E) to a stop codon at amino acid position 435. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). Based on the available evidence, this alteration is classified as pathogenic. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
MutationTaster
Benign
A
Vest4
GERP RS
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_DL_spliceai
Position offset: -9
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.