NM_000249.4(MLH1):c.1039-5T>C AND Colorectal cancer, hereditary nonpolyposis, type 2

Germline classification:: Benign/Likely benign (2 submissions)
Last evaluated:: Mar 13, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000410390.3

Allele description [Variation Report for NM_000249.4(MLH1):c.1039-5T>C]

NM_000249.4(MLH1):c.1039-5T>C

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.1039-5T>C

HGVS:

NC_000003.12:g.37025632T>C
NG_007109.2:g.37283T>C
NM_000249.4:c.1039-5T>CMANE SELECT
NM_001167617.3:c.745-5T>C
NM_001167618.3:c.316-5T>C
NM_001167619.3:c.316-5T>C
NM_001258271.2:c.1039-5T>C
NM_001258273.2:c.316-5T>C
NM_001258274.3:c.316-5T>C
NM_001354615.2:c.316-5T>C
NM_001354616.2:c.316-5T>C
NM_001354617.2:c.316-5T>C
NM_001354618.2:c.316-5T>C
NM_001354619.2:c.316-5T>C
NM_001354620.2:c.745-5T>C
NM_001354621.2:c.16-5T>C
NM_001354622.2:c.16-5T>C
NM_001354623.2:c.16-5T>C
NM_001354624.2:c.-36-5T>C
NM_001354625.2:c.-36-5T>C
NM_001354626.2:c.-36-5T>C
NM_001354627.2:c.-36-5T>C
NM_001354628.2:c.1039-5T>C
NM_001354629.2:c.940-5T>C
NM_001354630.2:c.1039-5T>C
LRG_216t1:c.1039-5T>C
LRG_216:g.37283T>C
NC_000003.11:g.37067123T>C
NM_000249.3:c.1039-5T>C

Links:

dbSNP: rs587782626

NCBI 1000 Genomes Browser:

rs587782626

Molecular consequence:

NM_000249.4:c.1039-5T>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001167617.3:c.745-5T>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001167618.3:c.316-5T>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001167619.3:c.316-5T>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001258271.2:c.1039-5T>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001258273.2:c.316-5T>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001258274.3:c.316-5T>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001354615.2:c.316-5T>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001354616.2:c.316-5T>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001354617.2:c.316-5T>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001354618.2:c.316-5T>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001354619.2:c.316-5T>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001354620.2:c.745-5T>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001354621.2:c.16-5T>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001354622.2:c.16-5T>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001354623.2:c.16-5T>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001354624.2:c.-36-5T>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001354625.2:c.-36-5T>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001354626.2:c.-36-5T>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001354627.2:c.-36-5T>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001354628.2:c.1039-5T>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001354629.2:c.940-5T>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001354630.2:c.1039-5T>C - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Name:: Colorectal cancer, hereditary nonpolyposis, type 2 (LYNCH2)
Synonyms:: COLON CANCER, FAMILIAL NONPOLYPOSIS, TYPE 2; Lynch syndrome II; MLH1-Related Lynch Syndrome; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0012249; MedGen: C1333991; Orphanet: 144; OMIM: 609310

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000489467	Counsyl	criteria provided, single submitter (Counsyl Autosomal Dominant Disease Classification criteria (2015))	Likely benign (Oct 18, 2016)	unknown	clinical testing	Counsyl Autosomal Dominant Disease Classification criteria (2015), Citation Link,
SCV004018095	Myriad Genetics, Inc.	criteria provided, single submitter (Myriad Autosomal Dominant, Autosomal Recessive and X-Linked Classification Criteria (2023))	Benign (Mar 13, 2023)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000489467

Counsyl

criteria provided, single submitter

(Counsyl Autosomal Dominant Disease Classification criteria (2015))

Likely benign
(Oct 18, 2016)

unknown

clinical testing

Counsyl Autosomal Dominant Disease Classification criteria (2015),

Citation Link,

SCV004018095

Myriad Genetics, Inc.

criteria provided, single submitter

(Myriad Autosomal Dominant, Autosomal Recessive and X-Linked Classification Criteria (2023))

Benign
(Mar 13, 2023)

unknown

clinical testing

PubMed (1)
[See all records that cite this PMID]

Citation Link

Help

Summary from all submissions

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

Citations

PubMed

Development and validation of a new algorithm for the reclassification of genetic variants identified in the BRCA1 and BRCA2 genes.

Pruss D, Morris B, Hughes E, Eggington JM, Esterling L, Robinson BS, van Kan A, Fernandes PH, Roa BB, Gutin A, Wenstrup RJ, Bowles KR.

Breast Cancer Res Treat. 2014 Aug;147(1):119-32. doi: 10.1007/s10549-014-3065-9. Epub 2014 Aug 2.

PubMed [citation]

PMID:: 25085752

Details of each submission

From Counsyl, SCV000489467.2

#	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., SCV004018095.1

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

Description

This variant is considered benign. This variant is intronic and is not expected to impact mRNA splicing. This variant is strongly associated with less severe personal and family histories of cancer, typical for individuals without pathogenic variants in this gene [PMID: 25085752].

#	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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