rs760939854
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_002691.4(POLD1):āc.77A>Gā(p.Asp26Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000761 in 1,444,624 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ). Synonymous variant affecting the same amino acid position (i.e. D26D) has been classified as Likely benign.
Frequency
Consequence
NM_002691.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
POLD1 | NM_002691.4 | c.77A>G | p.Asp26Gly | missense_variant | 2/27 | ENST00000440232.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
POLD1 | ENST00000440232.7 | c.77A>G | p.Asp26Gly | missense_variant | 2/27 | 1 | NM_002691.4 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000451 AC: 1AN: 221806Hom.: 0 AF XY: 0.00000842 AC XY: 1AN XY: 118822
GnomAD4 exome AF: 0.00000761 AC: 11AN: 1444624Hom.: 0 Cov.: 32 AF XY: 0.00000837 AC XY: 6AN XY: 716876
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Colorectal cancer, susceptibility to, 10 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 26, 2023 | This variant has not been reported in the literature in individuals affected with POLD1-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 26 of the POLD1 protein (p.Asp26Gly). ClinVar contains an entry for this variant (Variation ID: 537056). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at