chr7-44062819-T-G
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS1
The NM_000290.4(PGAM2):c.707A>C(p.Glu236Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000459 in 1,614,202 control chromosomes in the GnomAD database, including 9 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 0.00033 ( 1 hom., cov: 33)
Exomes 𝑓: 0.00047 ( 8 hom. )
Consequence
PGAM2
NM_000290.4 missense
NM_000290.4 missense
Scores
8
11
Clinical Significance
Conservation
PhyloP100: 7.79
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 -9 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.027874857).
BP6
?
Variant 7-44062819-T-G is Benign according to our data. Variant chr7-44062819-T-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 440991.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=3, not_provided=1, Uncertain_significance=1}.
BS1
?
Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.000472 (690/1461890) while in subpopulation MID AF= 0.0132 (76/5768). AF 95% confidence interval is 0.0108. There are 8 homozygotes in gnomad4_exome. There are 440 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PGAM2 | NM_000290.4 | c.707A>C | p.Glu236Ala | missense_variant | 3/3 | ENST00000297283.4 | |
DBNL | NM_001014436.3 | c.*1903T>G | 3_prime_UTR_variant | 13/13 | ENST00000448521.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PGAM2 | ENST00000297283.4 | c.707A>C | p.Glu236Ala | missense_variant | 3/3 | 1 | NM_000290.4 | P1 | |
DBNL | ENST00000448521.6 | c.*1903T>G | 3_prime_UTR_variant | 13/13 | 1 | NM_001014436.3 | P4 | ||
DBNL | ENST00000432854.5 | c.*1903T>G | 3_prime_UTR_variant | 11/11 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.000329 AC: 50AN: 152194Hom.: 1 Cov.: 33
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GnomAD3 exomes AF: 0.000696 AC: 175AN: 251420Hom.: 0 AF XY: 0.000964 AC XY: 131AN XY: 135894
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GnomAD4 exome AF: 0.000472 AC: 690AN: 1461890Hom.: 8 Cov.: 31 AF XY: 0.000605 AC XY: 440AN XY: 727244
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:3Other:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Glycogen storage disease type X Benign:2Other:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 20, 2024 | - - |
not provided, no classification provided | phenotyping only | GenomeConnect, ClinGen | - | GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. - |
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Apr 01, 2023 | - - |
PGAM2-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | May 25, 2022 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Uncertain
D
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
L
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D
REVEL
Uncertain
Sift
Benign
T
Sift4G
Benign
T
Polyphen
B
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