chr19-50402741-G-C
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_002691.4(POLD1):c.970G>C(p.Gly324Arg) variant causes a missense, splice region change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G324D) has been classified as Uncertain significance.
Frequency
Consequence
NM_002691.4 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
POLD1 | NM_002691.4 | c.970G>C | p.Gly324Arg | missense_variant, splice_region_variant | 8/27 | ENST00000440232.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
POLD1 | ENST00000440232.7 | c.970G>C | p.Gly324Arg | missense_variant, splice_region_variant | 8/27 | 1 | NM_002691.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD4 exome Cov.: 34
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
POLD1-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Dec 05, 2019 | The POLD1 c.970G>C (p.Gly324Arg) variant is a missense variant. A literature search was performed for the gene, cDNA change, and amino acid change. No publications were found based on this search. The p.Gly324Arg variant is not found in the Genome Aggregation Database, in a region of good sequence coverage, so is presumed to be rare. The Gly324 residue maps to the exonuclease domain of the protein. Based on the limited evidence, the p.Gly324Arg variant is classified as a variant of unknown significance for POLD1-related disorders. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at