NM_002691.4(POLD1):c.2275G>A (p.Val759Ile) AND Colorectal cancer, susceptibility to, 10

Germline classification:: Conflicting interpretations of pathogenicity (4 submissions)
Last evaluated:: Feb 1, 2024
Review status:: criteria provided, conflicting classifications

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000206687.26

Allele description [Variation Report for NM_002691.4(POLD1):c.2275G>A (p.Val759Ile)]

NM_002691.4(POLD1):c.2275G>A (p.Val759Ile)

Gene:

POLD1:DNA polymerase delta 1, catalytic subunit [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

19q13.33

Genomic location:

Preferred name:

NM_002691.4(POLD1):c.2275G>A (p.Val759Ile)

HGVS:

NC_000019.10:g.50413766G>A
NG_033800.1:g.34444G>A
NM_001256849.1:c.2275G>A
NM_001308632.1:c.2353G>A
NM_002691.4:c.2275G>AMANE SELECT
NP_001243778.1:p.Val759Ile
NP_001295561.1:p.Val785Ile
NP_002682.2:p.Val759Ile
LRG_785t1:c.2275G>A
LRG_785t2:c.2353G>A
LRG_785:g.34444G>A
LRG_785p1:p.Val759Ile
LRG_785p2:p.Val785Ile
NC_000019.9:g.50917023G>A
NM_002691.2:c.2275G>A
NM_002691.3:c.2275G>A
NR_046402.2:n.2320G>A

Protein change:

V759I

Links:

dbSNP: rs145473716

NCBI 1000 Genomes Browser:

rs145473716

Molecular consequence:

NM_001256849.1:c.2275G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001308632.1:c.2353G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_002691.4:c.2275G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_046402.2:n.2320G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Colorectal cancer, susceptibility to, 10
Synonyms:: COLORECTAL CANCER, SUSCEPTIBILITY TO, ON CHROMOSOME 19q; Colorectal cancer 10
Identifiers:: MONDO: MONDO:0012953; MedGen: C2675481; Orphanet: 220460; OMIM: 612591

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000262152	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Benign (Feb 1, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV000488800	Counsyl	criteria provided, single submitter (Counsyl Autosomal Dominant Disease Classification criteria (2015))	Uncertain significance (Jul 25, 2016)	unknown	clinical testing	PubMed (3) [See all records that cite these PMIDs] 27153395, 24123366, 23376243 Counsyl Autosomal Dominant Disease Classification criteria (2015), Citation Link,
SCV001141154	Mendelics	criteria provided, single submitter (Mendelics Assertion Criteria 2017)	Likely benign (May 28, 2019)	unknown	clinical testing	Citation Link,
SCV004018536	Myriad Genetics, Inc.	criteria provided, single submitter (Myriad Autosomal Dominant, Autosomal Recessive and X-Linked Classification Criteria (2023))	Uncertain significance (Apr 19, 2023)	unknown	clinical testing	Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Evaluation of ACMG-Guideline-Based Variant Classification of Cancer Susceptibility and Non-Cancer-Associated Genes in Families Affected by Breast Cancer.

Maxwell KN, Hart SN, Vijai J, Schrader KA, Slavin TP, Thomas T, Wubbenhorst B, Ravichandran V, Moore RM, Hu C, Guidugli L, Wenz B, Domchek SM, Robson ME, Szabo C, Neuhausen SL, Weitzel JN, Offit K, Couch FJ, Nathanson KL.

Am J Hum Genet. 2016 May 5;98(5):801-817. doi: 10.1016/j.ajhg.2016.02.024.

PubMed [citation]

PMID:: 27153395
PMCID:: PMC4863474

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000262152.10

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Counsyl, SCV000488800.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Mendelics, SCV001141154.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Myriad Genetics, Inc., SCV004018536.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

This variant is classified as a variant of uncertain significance as there is insufficient evidence to determine its impact on protein function and/or cancer risk.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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