19-50406167-G-T

Variant names:

• chr19-50406167-G-T
• rs3218763
• NM_002691.4:c.1243-15G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BP6_Very_Strong

The NM_002691.4(POLD1):​c.1243-15G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000261 in 1,609,750 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000024 (1 hom.)
• Consequence: POLD1 NM_002691.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.0510
• Publications: 1 publications found

Genes affected

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
• mandibular hypoplasia-deafness-progeroid syndrome

  Inheritance: AD, AR Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, Genomics England PanelApp, Ambry Genetics, Orphanet, G2P
• Polymerase proofreading-related adenomatous polyposis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• immunodeficiency 120

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics
• non-severe combined immunodeficiency due to polymerase delta deficiency

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 19-50406167-G-T is Benign according to our data. Variant chr19-50406167-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 513524.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50406167-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 513524.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50406167-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 513524.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50406167-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 513524.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50406167-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 513524.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50406167-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 513524.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50406167-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 513524.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50406167-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 513524.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50406167-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 513524.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50406167-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 513524.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50406167-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 513524.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50406167-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 513524.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50406167-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 513524.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50406167-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 513524.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50406167-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 513524.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50406167-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 513524.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50406167-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 513524.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50406167-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 513524.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50406167-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 513524.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50406167-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 513524.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50406167-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 513524.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50406167-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 513524.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50406167-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 513524.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50406167-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 513524.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50406167-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 513524.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50406167-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 513524.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50406167-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 513524.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50406167-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 513524.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50406167-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 513524.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50406167-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 513524.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50406167-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 513524.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50406167-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 513524.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50406167-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 513524.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50406167-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 513524.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50406167-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 513524.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50406167-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 513524.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50406167-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 513524.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50406167-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 513524.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50406167-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 513524.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50406167-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 513524.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50406167-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 513524.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50406167-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 513524.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50406167-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 513524.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POLD1	NM_002691.4	c.1243-15G>T		intron_variant	Intron 10 of 26	ENST00000440232.7	NP_002682.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POLD1	ENST00000440232.7	c.1243-15G>T		intron_variant	Intron 10 of 26	1	NM_002691.4	ENSP00000406046.1

Frequencies

GnomAD3 genomes AF: 0.0000460 AC: 7 AN: 152126 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000124 AC: 31 AN: 249568 AF XY: 0.000133

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000871

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.0000240 AC: 35 AN: 1457624 Hom.: 1 Cov.: 36 AF XY: 0.0000262 AC XY: 19 AN XY: 724472

African (AFR) AF: 0.00 AC: 0 AN: 33410

American (AMR) AF: 0.000718 AC: 32 AN: 44586

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25956

East Asian (EAS) AF: 0.00 AC: 0 AN: 39572

South Asian (SAS) AF: 0.00 AC: 0 AN: 86034

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53092

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5748

European-Non Finnish (NFE) AF: 9.02e-7 AC: 1 AN: 1109018

Other (OTH) AF: 0.0000332 AC: 2 AN: 60208

GnomAD4 genome AF: 0.0000460 AC: 7 AN: 152126 Hom.: 0 Cov.: 32 AF XY: 0.0000673 AC XY: 5 AN XY: 74304

African (AFR) AF: 0.0000483 AC: 2 AN: 41408

American (AMR) AF: 0.000327 AC: 5 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000434 Hom.: 0

Bravo AF: 0.0000529

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Colorectal cancer, susceptibility to, 10 Benign:2

Jan 23, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 05, 2025

Myriad Genetics, Inc.

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign. This variant is intronic and is not expected to impact mRNA splicing. -

not specified Benign:1

Nov 15, 2017

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided Benign:1

Mar 20, 2017

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.4
DANN	Benign	0.68
PhyloP100		0.051
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3218763; hg19: chr19-50909424;