NM_000249.4(MLH1):c.1732-9_1747delinsCC AND Hereditary cancer-predisposing syndrome

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: May 30, 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:: RCV002407435.2

Allele description [Variation Report for NM_000249.4(MLH1):c.1732-9_1747delinsCC]

NM_000249.4(MLH1):c.1732-9_1747delinsCC

Gene:

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

Variant type:

Indel

Cytogenetic location:

3p22.2

Genomic location:

Preferred name:

NM_000249.4(MLH1):c.1732-9_1747delinsCC

HGVS:

NC_000003.12:g.37047510_37047534delinsCC
NG_007109.2:g.59161_59185delinsCC
NM_000249.4:c.1732-9_1747delinsCCMANE SELECT
NM_001167617.3:c.1438-9_1453delinsCC
NM_001167618.3:c.1009-9_1024delinsCC
NM_001167619.3:c.1009-9_1024delinsCC
NM_001258271.2:c.1732-9_1747delinsCC
NM_001258273.2:c.1009-9_1024delinsCC
NM_001258274.3:c.1009-9_1024delinsCC
NM_001354615.2:c.1009-9_1024delinsCC
NM_001354616.2:c.1009-9_1024delinsCC
NM_001354617.2:c.1009-9_1024delinsCC
NM_001354618.2:c.1009-9_1024delinsCC
NM_001354619.2:c.1009-9_1024delinsCC
NM_001354620.2:c.1438-9_1453delinsCC
NM_001354621.2:c.709-9_724delinsCC
NM_001354622.2:c.709-9_724delinsCC
NM_001354623.2:c.709-9_724delinsCC
NM_001354624.2:c.658-9_673delinsCC
NM_001354625.2:c.658-9_673delinsCC
NM_001354626.2:c.658-9_673delinsCC
NM_001354627.2:c.658-9_673delinsCC
NM_001354628.2:c.1732-9_1747delinsCC
NM_001354629.2:c.1633-9_1648delinsCC
NM_001354630.2:c.1732-1007_1732-983delinsCC
LRG_216t1:c.1732-9_1747del25insCC
LRG_216:g.59161_59185delinsCC
NC_000003.11:g.37089001_37089025delinsCC
NM_000249.3:c.1732-9_1747del25insCC

Molecular consequence:

NM_001354630.2:c.1732-1007_1732-983delinsCC - intron variant - [Sequence Ontology: SO:0001627]
NM_000249.4:c.1732-9_1747delinsCC - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001167617.3:c.1438-9_1453delinsCC - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001167618.3:c.1009-9_1024delinsCC - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001167619.3:c.1009-9_1024delinsCC - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001258271.2:c.1732-9_1747delinsCC - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001258273.2:c.1009-9_1024delinsCC - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001258274.3:c.1009-9_1024delinsCC - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001354615.2:c.1009-9_1024delinsCC - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001354616.2:c.1009-9_1024delinsCC - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001354617.2:c.1009-9_1024delinsCC - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001354618.2:c.1009-9_1024delinsCC - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001354619.2:c.1009-9_1024delinsCC - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001354620.2:c.1438-9_1453delinsCC - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001354621.2:c.709-9_724delinsCC - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001354622.2:c.709-9_724delinsCC - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001354623.2:c.709-9_724delinsCC - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001354624.2:c.658-9_673delinsCC - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001354625.2:c.658-9_673delinsCC - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001354626.2:c.658-9_673delinsCC - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001354627.2:c.658-9_673delinsCC - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001354628.2:c.1732-9_1747delinsCC - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001354629.2:c.1633-9_1648delinsCC - 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
SCV002715693	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Likely pathogenic (May 30, 2019)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002715693

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Likely pathogenic
(May 30, 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, SCV002715693.2

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

Description

The c.1732-9_1747del25insCC variant, located at the boundary of intron 15 and exon 16, results from the deletion of 25 nucleotides (TCTTCCTAGGAGCCAGCACCGCTCT) at positions 1732-9 to 1747. This nucleotide region is highly conserved through gibbon. Using the BDGP, ESEfinder, and HSF splice site prediction tools, this alteration is expected to abolish the native splice acceptor site; however, experimental evidence is not currently available. 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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