19-50413824-C-T
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_ModerateBP6_Very_StrongBS2
The NM_002691.4(POLD1):c.2333C>T(p.Ala778Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000478 in 1,612,066 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_002691.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -14 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
POLD1 | NM_002691.4 | c.2333C>T | p.Ala778Val | missense_variant | Exon 19 of 27 | ENST00000440232.7 | NP_002682.2 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000328 AC: 5AN: 152248Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000117 AC: 29AN: 248902Hom.: 0 AF XY: 0.000149 AC XY: 20AN XY: 134606
GnomAD4 exome AF: 0.0000493 AC: 72AN: 1459700Hom.: 2 Cov.: 31 AF XY: 0.0000675 AC XY: 49AN XY: 726168
GnomAD4 genome AF: 0.0000328 AC: 5AN: 152366Hom.: 0 Cov.: 33 AF XY: 0.0000268 AC XY: 2AN XY: 74510
ClinVar
Submissions by phenotype
Colorectal cancer, susceptibility to, 10 Benign:2
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POLD1-related disorder Benign:1
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
Hereditary cancer-predisposing syndrome Benign:1
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at