NM_002528.7(NTHL1):c.232del (p.Val78fs) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Feb 6, 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:: RCV002551789.3

Allele description [Variation Report for NM_002528.7(NTHL1):c.232del (p.Val78fs)]

NM_002528.7(NTHL1):c.232del (p.Val78fs)

Gene:

NTHL1:nth like DNA glycosylase 1 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

16p13.3

Genomic location:

Preferred name:

NM_002528.7(NTHL1):c.232del (p.Val78fs)

HGVS:

NC_000016.10:g.2046250del
NG_005895.1:g.1945del
NG_008412.1:g.6617del
NM_001318193.2:c.232del
NM_001318194.2:c.24+30del
NM_002528.7:c.232delMANE SELECT
NP_001305122.2:p.Val78fs
NP_002519.2:p.Val78fs
LRG_1366t1:c.232del
LRG_1366:g.6617del
LRG_1366p1:p.Val78fs
LRG_487:g.1945del
NC_000016.9:g.2096251del
NC_000016.9:g.2096251del
NM_002528.5:c.256delG

Protein change:

V78fs

Links:

dbSNP: rs1314290585

NCBI 1000 Genomes Browser:

rs1314290585

Molecular consequence:

NM_001318193.2:c.232del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_002528.7:c.232del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001318194.2:c.24+30del - intron variant - [Sequence Ontology: SO:0001627]

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
SCV002929499	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Feb 6, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 25938944, 26559593, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002929499

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Feb 6, 2022)

germline

clinical testing

PubMed (3)
[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

A germline homozygous mutation in the base-excision repair gene NTHL1 causes adenomatous polyposis and colorectal cancer.

Weren RD, Ligtenberg MJ, Kets CM, de Voer RM, Verwiel ET, Spruijt L, van Zelst-Stams WA, Jongmans MC, Gilissen C, Hehir-Kwa JY, Hoischen A, Shendure J, Boyle EA, Kamping EJ, Nagtegaal ID, Tops BB, Nagengast FM, Geurts van Kessel A, van Krieken JH, Kuiper RP, Hoogerbrugge N.

Nat Genet. 2015 Jun;47(6):668-71. doi: 10.1038/ng.3287. Epub 2015 May 4.

PubMed [citation]

PMID:: 25938944

Biallelic NTHL1 Mutations in a Woman with Multiple Primary Tumors.

Rivera B, Castellsagué E, Bah I, van Kempen LC, Foulkes WD.

N Engl J Med. 2015 Nov 12;373(20):1985-6. doi: 10.1056/NEJMc1506878. Erratum in: N Engl J Med. 2015 Dec 17;373(25):e33. doi: 10.1056/NEJMx150043.

PubMed [citation]

PMID:: 26559593

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002929499.2

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

Description

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 821502). This variant has not been reported in the literature in individuals affected with NTHL1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Val86Serfs*17) in the NTHL1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in NTHL1 are known to be pathogenic (PMID: 25938944, 26559593).

#	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: Sep 29, 2024

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