rs1300269779
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Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP3
The NM_002691.4(POLD1):βc.125_136delβ(p.Glu42_Glu45del) variant causes a inframe deletion change. The variant allele was found at a frequency of 0.00000191 in 1,573,246 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (β β ).
Frequency
Genomes: π 0.0000066 ( 0 hom., cov: 32)
Exomes π: 0.0000014 ( 0 hom. )
Consequence
POLD1
NM_002691.4 inframe_deletion
NM_002691.4 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 5.42
Genes affected
POLD1 (HGNC:9175): (DNA polymerase delta 1, catalytic subunit) This gene encodes the 125-kDa catalytic subunit of DNA polymerase delta. DNA polymerase delta possesses both polymerase and 3' to 5' exonuclease activity and plays a critical role in DNA replication and repair. Alternatively spliced transcript variants have been observed for this gene, and a pseudogene of this gene is located on the long arm of chromosome 6. [provided by RefSeq, Mar 2012]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
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Very rare variant in population databases, with high coverage;
BP3
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Nonframeshift variant in repetitive region in NM_002691.4
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
POLD1 | NM_002691.4 | c.125_136del | p.Glu42_Glu45del | inframe_deletion | 2/27 | ENST00000440232.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
POLD1 | ENST00000440232.7 | c.125_136del | p.Glu42_Glu45del | inframe_deletion | 2/27 | 1 | NM_002691.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152116Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.00000141 AC: 2AN: 1421130Hom.: 0 AF XY: 0.00000142 AC XY: 1AN XY: 702720
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Colorectal cancer, susceptibility to, 10 Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 19, 2023 | This variant, c.125_136del, results in the deletion of 4 amino acid(s) of the POLD1 protein (p.Glu42_Glu45del), 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 POLD1-related conditions. ClinVar contains an entry for this variant (Variation ID: 439249). 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. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Counsyl | Nov 08, 2017 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Quest Diagnostics Nichols Institute San Juan Capistrano | Dec 21, 2016 | - - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 06, 2020 | The c.125_136del12 variant (also known as p.E42_E45del) is located in coding exon 1 of the POLD1 gene. This variant results from an in-frame AGGAGATGGAGG deletion at nucleotide positions 125 to 136. This results in the in-frame deletion of 4 amino acids between codons 42 and 45. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at