rs1555793871
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_002691.4(POLD1):c.3243_3245delinsTGT(p.Met1081_Arg1082delinsIleVal) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 31)
Consequence
POLD1
NM_002691.4 missense
NM_002691.4 missense
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 6.83
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 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
POLD1 | NM_002691.4 | c.3243_3245delinsTGT | p.Met1081_Arg1082delinsIleVal | missense_variant | 27/27 | ENST00000440232.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
POLD1 | ENST00000440232.7 | c.3243_3245delinsTGT | p.Met1081_Arg1082delinsIleVal | missense_variant | 27/27 | 1 | NM_002691.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD3 genomes
?
Cov.:
31
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? Cov.: 31
GnomAD4 genome
?
Cov.:
31
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Colorectal cancer, susceptibility to, 10 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 04, 2017 | In summary, this variant is a novel complex change with uncertain impact on protein function. 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. Experimental studies and prediction algorithms are not available for this complex variant, and the functional significance of replacing both amino acids is unknown. In addition, algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of both missense changes (p.Met1081Ile: SIFT: "Deleterious", PolyPhen-2: "Benign", Align-GVGD: "Class C0"; and p.Arg1082Val: SIFT: "Deleterious", PolyPhen-2: "Probably Damaging", Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with POLD1-related disease. This variant is not present in population databases (ExAC no frequency). This complex sequence change replaces methionine with isoleucine at codon 1081 and arginine with valine at codon 1082 of the POLD1 protein (p.Met1081_Arg1082delinsIleVal). The methionine residue at codon 1081 is highly conserved and there is a small physicochemical difference between methionine and isoleucine. The arginine residue at codon 1082 is highly conserved and there is a moderate physicochemical difference between arginine and valine. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at