NM_000179.3(MSH6):c.3848_3850dup (p.Ile1283dup) AND Hereditary nonpolyposis colorectal neoplasms

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 28, 2024
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:: RCV000461225.10

Allele description [Variation Report for NM_000179.3(MSH6):c.3848_3850dup (p.Ile1283dup)]

NM_000179.3(MSH6):c.3848_3850dup (p.Ile1283dup)

Gene:

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

Variant type:

Duplication

Cytogenetic location:

2p16.3

Genomic location:

Preferred name:

NM_000179.3(MSH6):c.3848_3850dup (p.Ile1283dup)

HGVS:

NC_000002.12:g.47806498_47806500dup
NG_007111.1:g.28352_28354dup
NG_008397.1:g.104178_104180dup
NM_000179.3:c.3848_3850dupMANE SELECT
NM_001281492.2:c.3458_3460dup
NM_001281493.2:c.2942_2944dup
NM_001281494.2:c.2942_2944dup
NP_000170.1:p.Ile1283dup
NP_000170.1:p.Ile1283dup
NP_001268421.1:p.Ile1153dup
NP_001268422.1:p.Ile981dup
NP_001268423.1:p.Ile981dup
LRG_219t1:c.3848_3850dup
LRG_219:g.28352_28354dup
LRG_219p1:p.Ile1283dup
NC_000002.11:g.48033634_48033635insTAT
NC_000002.11:g.48033637_48033639dup
NM_000179.2:c.3848_3850dup
NM_000179.2:c.3848_3850dupTTA
NM_000179.3:c.3848_3850dupTTAMANE SELECT

Links:

dbSNP: rs1553333420

NCBI 1000 Genomes Browser:

rs1553333420

Molecular consequence:

NM_000179.3:c.3848_3850dup - inframe_insertion - [Sequence Ontology: SO:0001821]
NM_001281492.2:c.3458_3460dup - inframe_insertion - [Sequence Ontology: SO:0001821]
NM_001281493.2:c.2942_2944dup - inframe_insertion - [Sequence Ontology: SO:0001821]
NM_001281494.2:c.2942_2944dup - inframe_insertion - [Sequence Ontology: SO:0001821]

Condition(s)

Name:: Hereditary nonpolyposis colorectal neoplasms
Identifiers:: MeSH: D003123; MedGen: C0009405

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000551297	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 28, 2024)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 24689082, 27601186, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000551297

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 28, 2024)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

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

A massive parallel sequencing workflow for diagnostic genetic testing of mismatch repair genes.

Hansen MF, Neckmann U, Lavik LA, Vold T, Gilde B, Toft RK, Sjursen W.

Mol Genet Genomic Med. 2014 Mar;2(2):186-200. doi: 10.1002/mgg3.62. Epub 2014 Jan 21.

PubMed [citation]

PMID:: 24689082
PMCID:: PMC3960061

Mismatch repair gene mutation spectrum in the Swedish Lynch syndrome population.

Lagerstedt-Robinson K, Rohlin A, Aravidis C, Melin B, Nordling M, Stenmark-Askmalm M, Lindblom A, Nilbert M.

Oncol Rep. 2016 Nov;36(5):2823-2835. doi: 10.3892/or.2016.5060. Epub 2016 Sep 1.

PubMed [citation]

PMID:: 27601186

See all PubMed Citations (3)

Details of each submission

From Invitae, SCV000551297.9

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This variant, c.3848_3850dup, results in the insertion of 1 amino acid(s) of the MSH6 protein (p.Ile1283dup), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs760500213, gnomAD 0.006%). This variant has been observed in individual(s) with Lynch syndrome (PMID: 24689082, 27601186). ClinVar contains an entry for this variant (Variation ID: 410530). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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 7, 2024

ClinVar

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