19-50407154-G-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_002691.4(POLD1):c.1666G>T(p.Val556Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,455,286 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Consequence
NM_002691.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
POLD1 | NM_002691.4 | c.1666G>T | p.Val556Leu | missense_variant | Exon 13 of 27 | ENST00000440232.7 | NP_002682.2 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD3 exomes AF: 0.00000404 AC: 1AN: 247428Hom.: 0 AF XY: 0.00000747 AC XY: 1AN XY: 133920
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1455286Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1AN XY: 722848
GnomAD4 genome Cov.: 31
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:1
The p.V556L variant (also known as c.1666G>T), located in coding exon 12 of the POLD1 gene, results from a G to T substitution at nucleotide position 1666. The valine at codon 556 is replaced by leucine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at