Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate
The NM_002691.4(POLD1):c.1893-4C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000207 in 1,449,792 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar 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: Likely_benign. The variant received -4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BP6
Variant 19-50409118-C-T is Benign according to our data. Variant chr19-50409118-C-T is described in CliVar as Likely_benign. Clinvar id is 469226.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-50409118-C-T is described in CliVar as Likely_benign. Clinvar id is 469226.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-50409118-C-T is described in CliVar as Likely_benign. Clinvar id is 469226.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-50409118-C-T is described in CliVar as Likely_benign. Clinvar id is 469226.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-50409118-C-T is described in CliVar as Likely_benign. Clinvar id is 469226.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-50409118-C-T is described in CliVar as Likely_benign. Clinvar id is 469226.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-50409118-C-T is described in CliVar as Likely_benign. Clinvar id is 469226.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-50409118-C-T is described in CliVar as Likely_benign. Clinvar id is 469226.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-50409118-C-T is described in CliVar as Likely_benign. Clinvar id is 469226.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-50409118-C-T is described in CliVar as Likely_benign. Clinvar id is 469226.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-50409118-C-T is described in CliVar as Likely_benign. Clinvar id is 469226.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-50409118-C-T is described in CliVar as Likely_benign. Clinvar id is 469226.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-50409118-C-T is described in CliVar as Likely_benign. Clinvar id is 469226.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-50409118-C-T is described in CliVar as Likely_benign. Clinvar id is 469226.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-50409118-C-T is described in CliVar as Likely_benign. Clinvar id is 469226.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-50409118-C-T is described in CliVar as Likely_benign. Clinvar id is 469226.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-50409118-C-T is described in CliVar as Likely_benign. Clinvar id is 469226.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-50409118-C-T is described in CliVar as Likely_benign. Clinvar id is 469226.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-50409118-C-T is described in CliVar as Likely_benign. Clinvar id is 469226.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-50409118-C-T is described in CliVar as Likely_benign. Clinvar id is 469226.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-50409118-C-T is described in CliVar as Likely_benign. Clinvar id is 469226.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-50409118-C-T is described in CliVar as Likely_benign. Clinvar id is 469226.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-50409118-C-T is described in CliVar as Likely_benign. Clinvar id is 469226.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-50409118-C-T is described in CliVar as Likely_benign. Clinvar id is 469226.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-50409118-C-T is described in CliVar as Likely_benign. Clinvar id is 469226.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-50409118-C-T is described in CliVar as Likely_benign. Clinvar id is 469226.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-50409118-C-T is described in CliVar as Likely_benign. Clinvar id is 469226.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-50409118-C-T is described in CliVar as Likely_benign. Clinvar id is 469226.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-50409118-C-T is described in CliVar as Likely_benign. Clinvar id is 469226.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-50409118-C-T is described in CliVar as Likely_benign. Clinvar id is 469226.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-50409118-C-T is described in CliVar as Likely_benign. Clinvar id is 469226.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-50409118-C-T is described in CliVar as Likely_benign. Clinvar id is 469226.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-50409118-C-T is described in CliVar as Likely_benign. Clinvar id is 469226.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-50409118-C-T is described in CliVar as Likely_benign. Clinvar id is 469226.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-50409118-C-T is described in CliVar as Likely_benign. Clinvar id is 469226.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-50409118-C-T is described in CliVar as Likely_benign. Clinvar id is 469226.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-50409118-C-T is described in CliVar as Likely_benign. Clinvar id is 469226.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-50409118-C-T is described in CliVar as Likely_benign. Clinvar id is 469226.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-50409118-C-T is described in CliVar as Likely_benign. Clinvar id is 469226.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-50409118-C-T is described in CliVar as Likely_benign. Clinvar id is 469226.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-50409118-C-T is described in CliVar as Likely_benign. Clinvar id is 469226.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-50409118-C-T is described in CliVar as Likely_benign. Clinvar id is 469226.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-50409118-C-T is described in CliVar as Likely_benign. Clinvar id is 469226.Status of the report is criteria_provided_single_submitter, 1 stars.