Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_ModerateBP6_Very_StrongBP7
The NM_002691.4(POLD1):c.2712C>T(p.Ala904Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000323 in 1,610,822 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 Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. A904A) has been classified as Likely benign.
POLD1 (HGNC:9175): (DNA polymerase delta 1, catalytic subunit) This gene encodes the 125-kDa catalytic subunit of DNA polymerase delta. DNA polymerase delta possesses both polymerase and 3' to 5' exonuclease activity and plays a critical role in DNA replication and repair. Alternatively spliced transcript variants have been observed for this gene, and a pseudogene of this gene is located on the long arm of chromosome 6. [provided by RefSeq, Mar 2012]
POLD1 Gene-Disease associations (from GenCC):
POLD1-related polyposis and colorectal cancer syndrome
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
colorectal cancer, susceptibility to, 10
Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Genomics England PanelApp
Our verdict: Benign. The variant received -11 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.34).
BP6
Variant 19-50415585-C-T is Benign according to our data. Variant chr19-50415585-C-T is described in CliVar as Likely_benign. Clinvar id is 469288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50415585-C-T is described in CliVar as Likely_benign. Clinvar id is 469288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50415585-C-T is described in CliVar as Likely_benign. Clinvar id is 469288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50415585-C-T is described in CliVar as Likely_benign. Clinvar id is 469288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50415585-C-T is described in CliVar as Likely_benign. Clinvar id is 469288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50415585-C-T is described in CliVar as Likely_benign. Clinvar id is 469288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50415585-C-T is described in CliVar as Likely_benign. Clinvar id is 469288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50415585-C-T is described in CliVar as Likely_benign. Clinvar id is 469288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50415585-C-T is described in CliVar as Likely_benign. Clinvar id is 469288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50415585-C-T is described in CliVar as Likely_benign. Clinvar id is 469288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50415585-C-T is described in CliVar as Likely_benign. Clinvar id is 469288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50415585-C-T is described in CliVar as Likely_benign. Clinvar id is 469288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50415585-C-T is described in CliVar as Likely_benign. Clinvar id is 469288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50415585-C-T is described in CliVar as Likely_benign. Clinvar id is 469288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50415585-C-T is described in CliVar as Likely_benign. Clinvar id is 469288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50415585-C-T is described in CliVar as Likely_benign. Clinvar id is 469288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50415585-C-T is described in CliVar as Likely_benign. Clinvar id is 469288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50415585-C-T is described in CliVar as Likely_benign. Clinvar id is 469288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50415585-C-T is described in CliVar as Likely_benign. Clinvar id is 469288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50415585-C-T is described in CliVar as Likely_benign. Clinvar id is 469288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50415585-C-T is described in CliVar as Likely_benign. Clinvar id is 469288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50415585-C-T is described in CliVar as Likely_benign. Clinvar id is 469288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50415585-C-T is described in CliVar as Likely_benign. Clinvar id is 469288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50415585-C-T is described in CliVar as Likely_benign. Clinvar id is 469288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50415585-C-T is described in CliVar as Likely_benign. Clinvar id is 469288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50415585-C-T is described in CliVar as Likely_benign. Clinvar id is 469288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50415585-C-T is described in CliVar as Likely_benign. Clinvar id is 469288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50415585-C-T is described in CliVar as Likely_benign. Clinvar id is 469288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50415585-C-T is described in CliVar as Likely_benign. Clinvar id is 469288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50415585-C-T is described in CliVar as Likely_benign. Clinvar id is 469288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50415585-C-T is described in CliVar as Likely_benign. Clinvar id is 469288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50415585-C-T is described in CliVar as Likely_benign. Clinvar id is 469288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50415585-C-T is described in CliVar as Likely_benign. Clinvar id is 469288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50415585-C-T is described in CliVar as Likely_benign. Clinvar id is 469288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50415585-C-T is described in CliVar as Likely_benign. Clinvar id is 469288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50415585-C-T is described in CliVar as Likely_benign. Clinvar id is 469288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50415585-C-T is described in CliVar as Likely_benign. Clinvar id is 469288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50415585-C-T is described in CliVar as Likely_benign. Clinvar id is 469288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50415585-C-T is described in CliVar as Likely_benign. Clinvar id is 469288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50415585-C-T is described in CliVar as Likely_benign. Clinvar id is 469288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50415585-C-T is described in CliVar as Likely_benign. Clinvar id is 469288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50415585-C-T is described in CliVar as Likely_benign. Clinvar id is 469288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50415585-C-T is described in CliVar as Likely_benign. Clinvar id is 469288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50415585-C-T is described in CliVar as Likely_benign. Clinvar id is 469288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50415585-C-T is described in CliVar as Likely_benign. Clinvar id is 469288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-1.25 with no splicing effect.
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. -