rs77938727
Positions:
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 1P and 13B. PP3BP4_StrongBP6BS1BS2
The NM_000290.4(PGAM2):c.290G>A(p.Gly97Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00052 in 1,613,944 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.00047 ( 1 hom., cov: 33)
Exomes 𝑓: 0.00053 ( 10 hom. )
Consequence
PGAM2
NM_000290.4 missense
NM_000290.4 missense
Scores
11
4
3
Clinical Significance
Conservation
PhyloP100: 7.68
Genes affected
PGAM2 (HGNC:8889): (phosphoglycerate mutase 2) Phosphoglycerate mutase (PGAM) catalyzes the reversible reaction of 3-phosphoglycerate (3-PGA) to 2-phosphoglycerate (2-PGA) in the glycolytic pathway. The PGAM is a dimeric enzyme containing, in different tissues, different proportions of a slow-migrating muscle (MM) isozyme, a fast-migrating brain (BB) isozyme, and a hybrid form (MB). This gene encodes muscle-specific PGAM subunit. Mutations in this gene cause muscle phosphoglycerate mutase eficiency, also known as glycogen storage disease X. [provided by RefSeq, Sep 2009]
DBNL (HGNC:2696): (drebrin like) Enables cadherin binding activity. Predicted to be involved in several processes, including Rac protein signal transduction; nervous system development; and podosome assembly. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
PP3
?
Multiple lines of computational evidence support a deleterious effect 8: AlphaMissense, BayesDel_noAF, Eigen, MutationAssessor, phyloP100way_vertebrate, PrimateAI, PROVEAN, REVEL [when max_spliceai, FATHMM_MKL, MetaRNN, MutationTaster was below the threshold]
BP4
?
Computational evidence support a benign effect (MetaRNN=0.017124146).
BP6
?
Variant 7-44065240-C-T is Benign according to our data. Variant chr7-44065240-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 421.We mark this variant Likely_benign, oryginal submissions are: {Benign=3, Uncertain_significance=1}.
BS1
?
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000466 (71/152348) while in subpopulation EAS AF= 0.0125 (65/5182). AF 95% confidence interval is 0.0101. There are 1 homozygotes in gnomad4. There are 38 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAdExome4 at 10 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PGAM2 | NM_000290.4 | c.290G>A | p.Gly97Asp | missense_variant | 1/3 | ENST00000297283.4 | |
DBNL | NM_001014436.3 | c.*4324C>T | 3_prime_UTR_variant | 13/13 | ENST00000448521.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PGAM2 | ENST00000297283.4 | c.290G>A | p.Gly97Asp | missense_variant | 1/3 | 1 | NM_000290.4 | P1 | |
DBNL | ENST00000448521.6 | c.*4324C>T | 3_prime_UTR_variant | 13/13 | 1 | NM_001014436.3 | P4 | ||
ENST00000445938.1 | n.333C>T | non_coding_transcript_exon_variant | 1/2 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.000466 AC: 71AN: 152230Hom.: 1 Cov.: 33
GnomAD3 genomes
?
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GnomAD3 exomes AF: 0.00125 AC: 314AN: 251144Hom.: 5 AF XY: 0.00114 AC XY: 155AN XY: 135818
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GnomAD4 exome AF: 0.000525 AC: 768AN: 1461596Hom.: 10 Cov.: 34 AF XY: 0.000525 AC XY: 382AN XY: 727132
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GnomAD4 genome ? AF: 0.000466 AC: 71AN: 152348Hom.: 1 Cov.: 33 AF XY: 0.000510 AC XY: 38AN XY: 74494
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Pathogenic:1Uncertain:1Benign:3
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Glycogen storage disease type X Pathogenic:1Uncertain:1Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Oct 13, 2022 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign. - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Oct 01, 1999 | - - |
Uncertain significance, criteria provided, single submitter | reference population | Soonchunhyang University Bucheon Hospital, Soonchunhyang University Medical Center | Mar 18, 2016 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 17, 2021 | This variant is associated with the following publications: (PMID: 6308514, 30445427, 10545043, 22995991, 8447317) - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Pathogenic
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Pathogenic
D
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T
MetaRNN
Benign
T
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
M
MutationTaster
Benign
A
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D
REVEL
Pathogenic
Sift
Pathogenic
D
Sift4G
Uncertain
D
Polyphen
P
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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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