NM_006231.4(POLE):c.899del (p.Ile300fs) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: May 27, 2022
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV003656577.1

Allele description [Variation Report for NM_006231.4(POLE):c.899del (p.Ile300fs)]

NM_006231.4(POLE):c.899del (p.Ile300fs)

Gene:

POLE:DNA polymerase epsilon, catalytic subunit [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

12q24.33

Genomic location:

Preferred name:

NM_006231.4(POLE):c.899del (p.Ile300fs)

HGVS:

NC_000012.12:g.132676556del
NG_033840.1:g.15969del
NM_006231.4:c.899delMANE SELECT
NP_006222.2:p.Ile300fs
LRG_789t1:c.899del
LRG_789:g.15969del
NC_000012.11:g.133253142del
NM_006231.3:c.899del

Protein change:

I300fs

Links:

dbSNP: rs2043057258

NCBI 1000 Genomes Browser:

rs2043057258

Molecular consequence:

NM_006231.4:c.899del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001392596	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (May 27, 2022)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 23230001, 25948378, 30503519, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001392596

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(May 27, 2022)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

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

Citations

PubMed

Polymerase ε1 mutation in a human syndrome with facial dysmorphism, immunodeficiency, livedo, and short stature ("FILS syndrome").

Pachlopnik Schmid J, Lemoine R, Nehme N, Cormier-Daire V, Revy P, Debeurme F, Debré M, Nitschke P, Bole-Feysot C, Legeai-Mallet L, Lim A, de Villartay JP, Picard C, Durandy A, Fischer A, de Saint Basile G.

J Exp Med. 2012 Dec 17;209(13):2323-30. doi: 10.1084/jem.20121303. Epub 2012 Dec 10.

PubMed [citation]

PMID:: 23230001
PMCID:: PMC3526359

A patient with polymerase E1 deficiency (POLE1): clinical features and overlap with DNA breakage/instability syndromes.

Thiffault I, Saunders C, Jenkins J, Raje N, Canty K, Sharma M, Grote L, Welsh HI, Farrow E, Twist G, Miller N, Zwick D, Zellmer L, Kingsmore SF, Safina NP.

BMC Med Genet. 2015 May 7;16:31. doi: 10.1186/s12881-015-0177-y.

PubMed [citation]

PMID:: 25948378
PMCID:: PMC4630961

See all PubMed Citations (4)

Details of each submission

From Invitae, SCV001392596.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 949191). This variant has not been reported in the literature in individuals affected with POLE-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ile300Thrfs*44) in the POLE gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in POLE are known to be pathogenic (PMID: 23230001, 25948378, 30503519).

#	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

Last Updated: Apr 20, 2024

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