NM_000249.4(MLH1):c.1668-2del AND Hereditary cancer-predisposing syndrome

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Aug 2, 2019
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:: RCV002403920.2

Allele description [Variation Report for NM_000249.4(MLH1):c.1668-2del]

NM_000249.4(MLH1):c.1668-2del

Gene:

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

Variant type:

Deletion

Cytogenetic location:

3p22.2

Genomic location:

Preferred name:

NM_000249.4(MLH1):c.1668-2del

HGVS:

NC_000003.12:g.37042266del
NG_007109.2:g.53917del
NM_000249.4:c.1668-2delMANE SELECT
NM_001167617.3:c.1374-2del
NM_001167618.3:c.945-2del
NM_001167619.3:c.945-2del
NM_001258271.2:c.1668-2del
NM_001258273.2:c.945-2del
NM_001258274.3:c.945-2del
NM_001354615.2:c.945-2del
NM_001354616.2:c.945-2del
NM_001354617.2:c.945-2del
NM_001354618.2:c.945-2del
NM_001354619.2:c.945-2del
NM_001354620.2:c.1374-2del
NM_001354621.2:c.645-2del
NM_001354622.2:c.645-2del
NM_001354623.2:c.645-2del
NM_001354624.2:c.594-2del
NM_001354625.2:c.594-2del
NM_001354626.2:c.594-2del
NM_001354627.2:c.594-2del
NM_001354628.2:c.1668-2del
NM_001354629.2:c.1569-2del
NM_001354630.2:c.1668-2del
LRG_216t1:c.1668-2del
LRG_216:g.53917del
NC_000003.11:g.37083757del
NM_000249.3:c.1668-2delA

Molecular consequence:

NM_000249.4:c.1668-2del - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001167617.3:c.1374-2del - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001167618.3:c.945-2del - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001167619.3:c.945-2del - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001258271.2:c.1668-2del - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001258273.2:c.945-2del - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001258274.3:c.945-2del - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001354615.2:c.945-2del - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001354616.2:c.945-2del - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001354617.2:c.945-2del - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001354618.2:c.945-2del - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001354619.2:c.945-2del - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001354620.2:c.1374-2del - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001354621.2:c.645-2del - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001354622.2:c.645-2del - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001354623.2:c.645-2del - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001354624.2:c.594-2del - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001354625.2:c.594-2del - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001354626.2:c.594-2del - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001354627.2:c.594-2del - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001354628.2:c.1668-2del - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001354629.2:c.1569-2del - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001354630.2:c.1668-2del - splice acceptor variant - [Sequence Ontology: SO:0001574]

Condition(s)

Name:: Hereditary cancer-predisposing syndrome
Synonyms:: Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002709211	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Likely pathogenic (Aug 2, 2019)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002709211

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Likely pathogenic
(Aug 2, 2019)

germline

clinical testing

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

Details of each submission

From Ambry Genetics, SCV002709211.2

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

Description

The c.1668-2delA intronic variant, located in intron 14 of the MLH1 gene, results from a deletion of one nucleotide within intron 14 of the MLH1 gene. This nucleotide position is highly conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is predicted to abolish the native splice acceptor site; however, direct evidence is unavailable. Alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. As such, this alteration is classified as likely pathogenic.

#	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: May 1, 2024

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