19-50406167-G-A

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 2P and 12B. PM2 BP4_Strong BP6_Very_Strong

The NM_002691.4(POLD1):​c.1243-15G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: POLD1 NM_002691.4 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• 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 -10 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 19-50406167-G-A is Benign according to our data. Variant chr19-50406167-G-A is described in CliVar as Likely_benign. Clinvar id is 1580918.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50406167-G-A is described in CliVar as Likely_benign. Clinvar id is 1580918.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50406167-G-A is described in CliVar as Likely_benign. Clinvar id is 1580918.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50406167-G-A is described in CliVar as Likely_benign. Clinvar id is 1580918.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50406167-G-A is described in CliVar as Likely_benign. Clinvar id is 1580918.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50406167-G-A is described in CliVar as Likely_benign. Clinvar id is 1580918.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50406167-G-A is described in CliVar as Likely_benign. Clinvar id is 1580918.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50406167-G-A is described in CliVar as Likely_benign. Clinvar id is 1580918.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50406167-G-A is described in CliVar as Likely_benign. Clinvar id is 1580918.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50406167-G-A is described in CliVar as Likely_benign. Clinvar id is 1580918.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50406167-G-A is described in CliVar as Likely_benign. Clinvar id is 1580918.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50406167-G-A is described in CliVar as Likely_benign. Clinvar id is 1580918.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50406167-G-A is described in CliVar as Likely_benign. Clinvar id is 1580918.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50406167-G-A is described in CliVar as Likely_benign. Clinvar id is 1580918.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50406167-G-A is described in CliVar as Likely_benign. Clinvar id is 1580918.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50406167-G-A is described in CliVar as Likely_benign. Clinvar id is 1580918.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50406167-G-A is described in CliVar as Likely_benign. Clinvar id is 1580918.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50406167-G-A is described in CliVar as Likely_benign. Clinvar id is 1580918.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50406167-G-A is described in CliVar as Likely_benign. Clinvar id is 1580918.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50406167-G-A is described in CliVar as Likely_benign. Clinvar id is 1580918.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50406167-G-A is described in CliVar as Likely_benign. Clinvar id is 1580918.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50406167-G-A is described in CliVar as Likely_benign. Clinvar id is 1580918.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50406167-G-A is described in CliVar as Likely_benign. Clinvar id is 1580918.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50406167-G-A is described in CliVar as Likely_benign. Clinvar id is 1580918.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50406167-G-A is described in CliVar as Likely_benign. Clinvar id is 1580918.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50406167-G-A is described in CliVar as Likely_benign. Clinvar id is 1580918.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50406167-G-A is described in CliVar as Likely_benign. Clinvar id is 1580918.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50406167-G-A is described in CliVar as Likely_benign. Clinvar id is 1580918.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50406167-G-A is described in CliVar as Likely_benign. Clinvar id is 1580918.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50406167-G-A is described in CliVar as Likely_benign. Clinvar id is 1580918.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50406167-G-A is described in CliVar as Likely_benign. Clinvar id is 1580918.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50406167-G-A is described in CliVar as Likely_benign. Clinvar id is 1580918.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50406167-G-A is described in CliVar as Likely_benign. Clinvar id is 1580918.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50406167-G-A is described in CliVar as Likely_benign. Clinvar id is 1580918.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50406167-G-A is described in CliVar as Likely_benign. Clinvar id is 1580918.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50406167-G-A is described in CliVar as Likely_benign. Clinvar id is 1580918.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50406167-G-A is described in CliVar as Likely_benign. Clinvar id is 1580918.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50406167-G-A is described in CliVar as Likely_benign. Clinvar id is 1580918.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50406167-G-A is described in CliVar as Likely_benign. Clinvar id is 1580918.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50406167-G-A is described in CliVar as Likely_benign. Clinvar id is 1580918.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50406167-G-A is described in CliVar as Likely_benign. Clinvar id is 1580918.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50406167-G-A is described in CliVar as Likely_benign. Clinvar id is 1580918.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50406167-G-A is described in CliVar as Likely_benign. Clinvar id is 1580918.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>A		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>A		intron_variant	Intron 10 of 26	1	NM_002691.4	ENSP00000406046.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00 AC: 0 AN: 249568 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

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: 0.00

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 32

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Colorectal cancer, susceptibility to, 10 Benign:2

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. -

Dec 24, 2024

Labcorp Genetics (formerly Invitae), Labcorp

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	2.2
DANN	Benign	0.65
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;