19-50406992-G-A
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_002691.4(POLD1):c.1504G>A(p.Asp502Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000425 in 1,435,618 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 Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D502E) has been classified as Likely benign.
Frequency
Consequence
NM_002691.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
POLD1 | NM_002691.4 | c.1504G>A | p.Asp502Asn | missense_variant | 13/27 | ENST00000440232.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
POLD1 | ENST00000440232.7 | c.1504G>A | p.Asp502Asn | missense_variant | 13/27 | 1 | NM_002691.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000341 AC: 5AN: 146796Hom.: 0 Cov.: 30
GnomAD3 exomes AF: 0.000212 AC: 51AN: 240080Hom.: 0 AF XY: 0.000177 AC XY: 23AN XY: 129920
GnomAD4 exome AF: 0.0000435 AC: 56AN: 1288822Hom.: 0 Cov.: 34 AF XY: 0.0000407 AC XY: 26AN XY: 638574
GnomAD4 genome AF: 0.0000341 AC: 5AN: 146796Hom.: 0 Cov.: 30 AF XY: 0.0000280 AC XY: 2AN XY: 71470
ClinVar
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Quest Diagnostics Nichols Institute San Juan Capistrano | Jun 29, 2022 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 30, 2020 | Has not been previously published as pathogenic or benign germline variant to our knowledge; This variant is associated with the following publications: (PMID: 7704014, 27161865, 10074927, 20951805, 24816253) - |
Hereditary cancer-predisposing syndrome Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 07, 2021 | 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. - |
Likely benign, criteria provided, single submitter | curation | Sema4, Sema4 | May 06, 2021 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Jul 01, 2019 | - - |
Colorectal cancer, susceptibility to, 10 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 18, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at