rs1060501809
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PM4_Supporting
The NM_002691.4(POLD1):c.885_887del(p.Val296del) variant causes a inframe deletion change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. V295V) has been classified as Likely benign.
Frequency
Genomes: not found (cov: 33)
Consequence
POLD1
NM_002691.4 inframe_deletion
NM_002691.4 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 4.27
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 3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PM4
?
Nonframeshift variant in NON repetitive region in NM_002691.4. Strenght limited to Supporting due to length of the change: 1aa.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
POLD1 | NM_002691.4 | c.885_887del | p.Val296del | inframe_deletion | 8/27 | ENST00000440232.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
POLD1 | ENST00000440232.7 | c.885_887del | p.Val296del | inframe_deletion | 8/27 | 1 | NM_002691.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | May 01, 2022 | Not observed at significant frequency in large population cohorts (gnomAD); In-frame deletion of 1 amino acid in a non-repeat region; Has not been previously published as pathogenic or benign to our knowledge - |
Colorectal cancer, susceptibility to, 10 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 23, 2016 | In summary, this variant is a novel single amino acid deletion with uncertain impact on mRNA splicing and protein function. It has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of sequence changes on mRNA splicing suggest that this variant may alter mRNA splicing, but this prediction has not been confirmed by published transcriptional studies. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a POLD1-related disease. This sequence change deletes 3 nucleotides from exon 8 of the POLD1 mRNA (c.885_887delGGT). This leads to the deletion of 1 amino acid residue in the POLD1 protein (p.Val296del) but otherwise preserves the integrity of the reading frame. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Name
Calibrated prediction
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Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at