NM_000249.4(MLH1):c.885-5G>T AND not specified

Germline classification:: Likely benign (1 submission)
Last evaluated:: Feb 6, 2023
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:: RCV000417381.7

Allele description [Variation Report for NM_000249.4(MLH1):c.885-5G>T]

NM_000249.4(MLH1):c.885-5G>T

Gene:

MLH1:mutL homolog 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

3p22.2

Genomic location:

Preferred name:

NM_000249.4(MLH1):c.885-5G>T

HGVS:

NC_000003.12:g.37020305G>T
NG_007109.2:g.31956G>T
NM_000249.4:c.885-5G>TMANE SELECT
NM_001167617.3:c.591-5G>T
NM_001167618.3:c.162-5G>T
NM_001167619.3:c.162-5G>T
NM_001258271.2:c.885-5G>T
NM_001258273.2:c.162-5G>T
NM_001258274.3:c.162-5G>T
NM_001354615.2:c.162-5G>T
NM_001354616.2:c.162-5G>T
NM_001354617.2:c.162-5G>T
NM_001354618.2:c.162-5G>T
NM_001354619.2:c.162-5G>T
NM_001354620.2:c.591-5G>T
NM_001354621.2:c.-139-5G>T
NM_001354622.2:c.-139-5G>T
NM_001354623.2:c.-139-5G>T
NM_001354624.2:c.-36-5332G>T
NM_001354625.2:c.-36-5332G>T
NM_001354626.2:c.-36-5332G>T
NM_001354627.2:c.-36-5332G>T
NM_001354628.2:c.885-5G>T
NM_001354629.2:c.786-5G>T
NM_001354630.2:c.885-5G>T
LRG_216t1:c.885-5G>T
LRG_216:g.31956G>T
NC_000003.11:g.37061796G>T
NM_000249.3:c.885-5G>T

Links:

dbSNP: rs267607802

NCBI 1000 Genomes Browser:

rs267607802

Molecular consequence:

NM_000249.4:c.885-5G>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001167617.3:c.591-5G>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001167618.3:c.162-5G>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001167619.3:c.162-5G>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001258271.2:c.885-5G>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001258273.2:c.162-5G>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001258274.3:c.162-5G>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001354615.2:c.162-5G>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001354616.2:c.162-5G>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001354617.2:c.162-5G>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001354618.2:c.162-5G>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001354619.2:c.162-5G>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001354620.2:c.591-5G>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001354621.2:c.-139-5G>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001354622.2:c.-139-5G>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001354623.2:c.-139-5G>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001354624.2:c.-36-5332G>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001354625.2:c.-36-5332G>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001354626.2:c.-36-5332G>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001354627.2:c.-36-5332G>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001354628.2:c.885-5G>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001354629.2:c.786-5G>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001354630.2:c.885-5G>T - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000696187	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Likely benign (Feb 6, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 12624141, 18561205 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000696187

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Likely benign
(Feb 6, 2023)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

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

Citations

PubMed

Cancer risk in 348 French MSH2 or MLH1 gene carriers.

Parc Y, Boisson C, Thomas G, Olschwang S.

J Med Genet. 2003 Mar;40(3):208-13. No abstract available.

PubMed [citation]

PMID:: 12624141
PMCID:: PMC1735402

A large fraction of unclassified variants of the mismatch repair genes MLH1 and MSH2 is associated with splicing defects.

Tournier I, Vezain M, Martins A, Charbonnier F, Baert-Desurmont S, Olschwang S, Wang Q, Buisine MP, Soret J, Tazi J, Frébourg T, Tosi M.

Hum Mutat. 2008 Dec;29(12):1412-24. doi: 10.1002/humu.20796.

PubMed [citation]

PMID:: 18561205

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000696187.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

Variant summary: MLH1 c.885-5G>T alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 4/4 computational tools predict no significant impact on normal splicing. Consistently, functional analysis using the pCAS ex vivo splicing assay and RNA analysis demonstrated this variant had no effect (Tournier_2008).The variant allele was found at a frequency of 2e-05 in 251406 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.885-5G>T has been reported in the literature in at-least one proband referred to a French family cancer clinic and satisfying at least one of the modified Amsterdam criteria (Parc_2003). These report(s) do not provide unequivocal conclusions about association of the variant with Hereditary Nonpolyposis Colorectal Cancer/Lynch syndrome. Seven clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as likely benign.

#	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: Oct 13, 2024

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