15-89333596-TTGCTGCTGCTGCTGCTGCTGCTGCTGCTGC-TTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGC
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP3BP6
The NM_001430120.1(POLGARF):c.196_213dupGCAGCAGCAGCAGCAGCA(p.Ala66_Ala71dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000144 in 1,598,000 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001430120.1 conservative_inframe_insertion
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
POLG | NM_002693.3 | c.141_158dupGCAGCAGCAGCAGCAGCA | p.Gln48_Gln53dup | disruptive_inframe_insertion | Exon 2 of 23 | ENST00000268124.11 | NP_002684.1 | |
POLGARF | NM_001430120.1 | c.196_213dupGCAGCAGCAGCAGCAGCA | p.Ala66_Ala71dup | conservative_inframe_insertion | Exon 1 of 2 | NP_001417049.1 | ||
POLG | NM_001126131.2 | c.141_158dupGCAGCAGCAGCAGCAGCA | p.Gln48_Gln53dup | disruptive_inframe_insertion | Exon 2 of 23 | NP_001119603.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
POLGARF | ENST00000706918.1 | c.196_213dupGCAGCAGCAGCAGCAGCA | p.Ala66_Ala71dup | conservative_inframe_insertion | Exon 1 of 2 | ENSP00000516626.1 | ||||
POLG | ENST00000268124.11 | c.141_158dupGCAGCAGCAGCAGCAGCA | p.Gln48_Gln53dup | disruptive_inframe_insertion | Exon 2 of 23 | 1 | NM_002693.3 | ENSP00000268124.5 |
Frequencies
GnomAD3 genomes AF: 0.0000132 AC: 2AN: 151604Hom.: 0 Cov.: 30
GnomAD4 exome AF: 0.0000145 AC: 21AN: 1446396Hom.: 0 Cov.: 31 AF XY: 0.0000125 AC XY: 9AN XY: 719198
GnomAD4 genome AF: 0.0000132 AC: 2AN: 151604Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 74046
ClinVar
Submissions by phenotype
POLG-related disorder Uncertain:1
The POLG c.141_158dup18 variant is predicted to result in an in-frame duplication (p.Gln50_Gln55dup). This variant is located in the glutamine (Gln) repeat region of exon 2 and to our knowledge, repeat variations in this region have not been reported to be conclusively related to human diseases in the literature. In ClinVar, these repeat variations were classified as a variant of uncertain significance or likely benign/benign (https://www.ncbi.nlm.nih.gov/clinvar/). Although we suspect this repeat variant is benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -
Progressive sclerosing poliodystrophy Uncertain:1
This variant, c.141_158dup, results in the insertion of 6 amino acid(s) of the POLG protein (p.Gln50_Gln55dup), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with POLG-related conditions. ClinVar contains an entry for this variant (Variation ID: 507643). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -
not provided Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at