NM_000249.4(MLH1):c.1039-1G>T AND Colorectal cancer, hereditary nonpolyposis, type 2

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: Jul 19, 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:: RCV002467460.3

Allele description [Variation Report for NM_000249.4(MLH1):c.1039-1G>T]

NM_000249.4(MLH1):c.1039-1G>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.1039-1G>T

HGVS:

NC_000003.12:g.37025636G>T
NG_007109.2:g.37287G>T
NM_000249.4:c.1039-1G>TMANE SELECT
NM_001167617.3:c.745-1G>T
NM_001167618.3:c.316-1G>T
NM_001167619.3:c.316-1G>T
NM_001258271.2:c.1039-1G>T
NM_001258273.2:c.316-1G>T
NM_001258274.3:c.316-1G>T
NM_001354615.2:c.316-1G>T
NM_001354616.2:c.316-1G>T
NM_001354617.2:c.316-1G>T
NM_001354618.2:c.316-1G>T
NM_001354619.2:c.316-1G>T
NM_001354620.2:c.745-1G>T
NM_001354621.2:c.16-1G>T
NM_001354622.2:c.16-1G>T
NM_001354623.2:c.16-1G>T
NM_001354624.2:c.-36-1G>T
NM_001354625.2:c.-36-1G>T
NM_001354626.2:c.-36-1G>T
NM_001354627.2:c.-36-1G>T
NM_001354628.2:c.1039-1G>T
NM_001354629.2:c.940-1G>T
NM_001354630.2:c.1039-1G>T
LRG_216t1:c.1039-1G>T
LRG_216:g.37287G>T
NC_000003.11:g.37067127G>T
NM_000249.3:c.1039-1G>T

Molecular consequence:

NM_000249.4:c.1039-1G>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001167617.3:c.745-1G>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001167618.3:c.316-1G>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001167619.3:c.316-1G>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001258271.2:c.1039-1G>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001258273.2:c.316-1G>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001258274.3:c.316-1G>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001354615.2:c.316-1G>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001354616.2:c.316-1G>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001354617.2:c.316-1G>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001354618.2:c.316-1G>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001354619.2:c.316-1G>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001354620.2:c.745-1G>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001354621.2:c.16-1G>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001354622.2:c.16-1G>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001354623.2:c.16-1G>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001354624.2:c.-36-1G>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001354625.2:c.-36-1G>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001354626.2:c.-36-1G>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001354627.2:c.-36-1G>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001354628.2:c.1039-1G>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001354629.2:c.940-1G>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001354630.2:c.1039-1G>T - splice acceptor variant - [Sequence Ontology: SO:0001574]

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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aminoglycoside phosphotransferase protein [Rhizobium sp. Kim5]
aminoglycoside phosphotransferase protein [Rhizobium sp. Kim5]
gi|1190826911|gnl|CCG|Kim5_CH00029| Q56164.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002762818	Centre for Mendelian Genomics, University Medical Centre Ljubljana	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Dec 9, 2022)	germline	research	PubMed (1) [See all records that cite this PMID]
SCV004189196	Myriad Genetics, Inc.	criteria provided, single submitter (Myriad Autosomal Dominant, Autosomal Recessive and X-Linked Classification Criteria (2023))	Likely pathogenic (Jul 19, 2023)	unknown	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002762818

Centre for Mendelian Genomics, University Medical Centre Ljubljana

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Dec 9, 2022)

germline

research

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

SCV004189196

Myriad Genetics, Inc.

criteria provided, single submitter

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

Likely pathogenic
(Jul 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	no	not provided	not provided	not provided	not provided	not provided	research
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Centre for Mendelian Genomics, University Medical Centre Ljubljana, SCV002762818.2

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

Description

PVS1, PS4_SUP, PM2_SUP

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	no	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Myriad Genetics, Inc., SCV004189196.1

#	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 considered likely pathogenic. This variant occurs within a consensus splice junction and is predicted to result in abnormal mRNA splicing of either an out-of-frame exon or an in-frame exon necessary for protein stability and/or normal function.

#	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: May 1, 2024

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