NM_000179.3(MSH6):c.3798_3801+9del AND Hereditary cancer-predisposing syndrome

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: Mar 26, 2024
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:: RCV000582277.13

Allele description [Variation Report for NM_000179.3(MSH6):c.3798_3801+9del]

NM_000179.3(MSH6):c.3798_3801+9del

Gene:

MSH6:mutS homolog 6 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

2p16.3

Genomic location:

Preferred name:

NM_000179.3(MSH6):c.3798_3801+9del

HGVS:

NC_000002.12:g.47806355_47806367del
NG_007111.1:g.28209_28221del
NG_008397.1:g.104311_104323del
NM_000179.2:c.3798_3801+9del13
NM_000179.3:c.3798_3801+9delMANE SELECT
NM_001281492.2:c.3408_3411+9del
NM_001281493.2:c.2892_2895+9del
NM_001281494.2:c.2892_2895+9del
LRG_219t1:c.3798_3801+9del
LRG_219:g.28209_28221del
NC_000002.11:g.48033492_48033504del
NC_000002.11:g.48033494_48033506del
NM_000179.2:c.3798_3801+9del
NM_000179.2:c.3798_3801+9del13
NM_000179.2:c.3798_3801+9delTATGGTATGTGCA

Links:

dbSNP: rs1553333168

NCBI 1000 Genomes Browser:

rs1553333168

Molecular consequence:

NM_000179.3:c.3798_3801+9del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001281492.2:c.3408_3411+9del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001281493.2:c.2892_2895+9del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001281494.2:c.2892_2895+9del - 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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000690399	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Apr 5, 2019)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002620126	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Mar 26, 2024)	germline	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

SCV000690399

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Apr 5, 2019)

germline

clinical testing

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

SCV002620126

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Mar 26, 2024)

germline

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	germline	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

Detection of DNA mismatch repair deficient crypts in random colonoscopic biopsies identifies Lynch syndrome patients.

Brand RE, Dudley B, Karloski E, Das R, Fuhrer K, Pai RK, Pai RK.

Fam Cancer. 2020 Apr;19(2):169-175. doi: 10.1007/s10689-020-00161-w.

PubMed [citation]

PMID:: 31997046

Details of each submission

From Color Diagnostics, LLC DBA Color Health, SCV000690399.3

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

#	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

From Ambry Genetics, SCV002620126.2

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

Description

The c.3798_3801+9del13 pathogenic mutation results from a deletion of 13 nucleotides between positions c.3798 and c.3801+9 and involves the canonical splice donor site after coding exon 8 of the MSH6 gene. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This variant has been observed in an affected individual from a cohort of Lynch Syndrome patients (Brand et al. Fam Cancer 2020 Apr;19(2):169-175). 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 interpreted as a disease-causing mutation.

#	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: Oct 26, 2024

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