15-89329112-T-TGAG
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Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP6
The NM_002693.3(POLG):c.856-3_856-2insCTC variant causes a splice region, splice polypyrimidine tract, intron change. The variant allele was found at a frequency of 0.0000143 in 1,610,370 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000014 ( 1 hom. )
Consequence
POLG
NM_002693.3 splice_region, splice_polypyrimidine_tract, intron
NM_002693.3 splice_region, splice_polypyrimidine_tract, intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 5.02
Genes affected
POLG (HGNC:9179): (DNA polymerase gamma, catalytic subunit) Mitochondrial DNA polymerase is heterotrimeric, consisting of a homodimer of accessory subunits plus a catalytic subunit. The protein encoded by this gene is the catalytic subunit of mitochondrial DNA polymerase. The encoded protein contains a polyglutamine tract near its N-terminus that may be polymorphic. Defects in this gene are a cause of progressive external ophthalmoplegia with mitochondrial DNA deletions 1 (PEOA1), sensory ataxic neuropathy dysarthria and ophthalmoparesis (SANDO), Alpers-Huttenlocher syndrome (AHS), and mitochondrial neurogastrointestinal encephalopathy syndrome (MNGIE). Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -1 ACMG points.
BP6
Variant 15-89329112-T-TGAG is Benign according to our data. Variant chr15-89329112-T-TGAG is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 1256102.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=1}.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
POLG | NM_002693.3 | c.856-3_856-2insCTC | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000268124.11 | |||
POLGARF | NM_001406557.1 | c.*128-3_*128-2insCTC | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ||||
POLG | NM_001126131.2 | c.856-3_856-2insCTC | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
POLG | ENST00000268124.11 | c.856-3_856-2insCTC | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_002693.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 151992Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000828 AC: 2AN: 241470Hom.: 0 AF XY: 0.0000153 AC XY: 2AN XY: 131084
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GnomAD4 exome AF: 0.0000137 AC: 20AN: 1458260Hom.: 1 Cov.: 33 AF XY: 0.0000152 AC XY: 11AN XY: 725394
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GnomAD4 genome AF: 0.0000197 AC: 3AN: 152110Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74374
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:2
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 15, 2021 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | Feb 16, 2021 | - - |
Progressive sclerosing poliodystrophy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 30, 2023 | - - |
Computational scores
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Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at