NM_000249.4(MLH1):c.207+5_207+8del AND Hereditary cancer-predisposing syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 3, 2020
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:: RCV002422125.2

Allele description [Variation Report for NM_000249.4(MLH1):c.207+5_207+8del]

NM_000249.4(MLH1):c.207+5_207+8del

Gene:

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

Variant type:

Microsatellite

Cytogenetic location:

3p22.2

Genomic location:

Preferred name:

NM_000249.4(MLH1):c.207+5_207+8del

HGVS:

NC_000003.12:g.36996710GTAA[1]
NG_007109.2:g.8361GTAA[1]
NG_008418.1:g.1588TTAC[1]
NM_000249.4:c.207+5_207+8delMANE SELECT
NM_001167617.3:c.-83+5_-83+8del
NM_001167618.3:c.-517+5_-517+8del
NM_001167619.3:c.-425+5_-425+8del
NM_001258271.2:c.207+5_207+8del
NM_001258273.2:c.-517+3051_-517+3054del
NM_001258274.3:c.-662+5_-662+8del
NM_001354615.2:c.-420+5_-420+8del
NM_001354616.2:c.-425+5_-425+8del
NM_001354617.2:c.-517+5_-517+8del
NM_001354618.2:c.-517+5_-517+8del
NM_001354619.2:c.-517+5_-517+8del
NM_001354620.2:c.-83+5_-83+8del
NM_001354621.2:c.-610+5_-610+8del
NM_001354622.2:c.-723+5_-723+8del
NM_001354623.2:c.-723+2824_-723+2827del
NM_001354624.2:c.-620+5_-620+8del
NM_001354625.2:c.-523+5_-523+8del
NM_001354626.2:c.-620+5_-620+8del
NM_001354627.2:c.-620+5_-620+8del
NM_001354628.2:c.207+5_207+8del
NM_001354629.2:c.207+5_207+8del
NM_001354630.2:c.207+5_207+8del
LRG_216t1:c.207+5_207+8del
LRG_216:g.8361GTAA[1]
NC_000003.11:g.37038201GTAA[1]
NM_000249.3:c.207+5_207+8delGTAA

Molecular consequence:

NM_001258273.2:c.-517+3051_-517+3054del - intron variant - [Sequence Ontology: SO:0001627]
NM_001354623.2:c.-723+2824_-723+2827del - intron variant - [Sequence Ontology: SO:0001627]
NM_000249.4:c.207+5_207+8del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001167617.3:c.-83+5_-83+8del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001167618.3:c.-517+5_-517+8del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001167619.3:c.-425+5_-425+8del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001258271.2:c.207+5_207+8del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001258274.3:c.-662+5_-662+8del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001354615.2:c.-420+5_-420+8del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001354616.2:c.-425+5_-425+8del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001354617.2:c.-517+5_-517+8del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001354618.2:c.-517+5_-517+8del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001354619.2:c.-517+5_-517+8del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001354620.2:c.-83+5_-83+8del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001354621.2:c.-610+5_-610+8del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001354622.2:c.-723+5_-723+8del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001354624.2:c.-620+5_-620+8del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001354625.2:c.-523+5_-523+8del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001354626.2:c.-620+5_-620+8del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001354627.2:c.-620+5_-620+8del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001354628.2:c.207+5_207+8del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001354629.2:c.207+5_207+8del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001354630.2:c.207+5_207+8del - splice donor variant - [Sequence Ontology: SO:0001575]

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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002727697	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Aug 3, 2020)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002727697

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Aug 3, 2020)

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, SCV002727697.2

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

Description

The c.207+5_+8delGTAA intronic variant is located 5 nucleotides after coding exon 2 of the MLH1 gene. This variant results from a deletion of 4 nucleotides in intron 2 between positions c.207+5 and c.207+8. Several of these nucleotide positions are not well conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice donor site; however, direct evidence is insufficient at this time (Ambry internal data). This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

#	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

ClinVar

Relating variation to medicine