NM_000179.3(MSH6):c.28T>A (p.Phe10Ile) AND Hereditary cancer-predisposing syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: May 3, 2023
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:: RCV003278515.2

Allele description [Variation Report for NM_000179.3(MSH6):c.28T>A (p.Phe10Ile)]

NM_000179.3(MSH6):c.28T>A (p.Phe10Ile)

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

2p16.3

Genomic location:

Preferred name:

NM_000179.3(MSH6):c.28T>A (p.Phe10Ile)

HGVS:

NC_000002.12:g.47783261T>A
NG_007111.1:g.5115T>A
NG_166732.1:g.644T>A
NM_000179.3:c.28T>AMANE SELECT
NM_001281492.2:c.28T>A
NM_001281493.2:c.-709T>A
NM_001406795.1:c.28T>A
NM_001406796.1:c.28T>A
NM_001406797.1:c.-38+30T>A
NM_001406798.1:c.28T>A
NM_001406799.1:c.-301T>A
NM_001406800.1:c.28T>A
NM_001406801.1:c.-38+30T>A
NM_001406802.1:c.28T>A
NM_001406803.1:c.28T>A
NM_001406804.1:c.-28T>A
NM_001406805.1:c.-38+30T>A
NM_001406806.1:c.-69+30T>A
NM_001406807.1:c.-901T>A
NM_001406808.1:c.28T>A
NM_001406809.1:c.28T>A
NM_001406811.1:c.-709T>A
NM_001406812.1:c.-556T>A
NM_001406813.1:c.28T>A
NM_001406814.1:c.-967T>A
NM_001406815.1:c.-280+30T>A
NM_001406816.1:c.-512T>A
NM_001406817.1:c.28T>A
NM_001407362.1:c.28T>A
NP_000170.1:p.Phe10Ile
NP_000170.1:p.Phe10Ile
NP_001268421.1:p.Phe10Ile
NP_001393724.1:p.Phe10Ile
NP_001393725.1:p.Phe10Ile
NP_001393727.1:p.Phe10Ile
NP_001393729.1:p.Phe10Ile
NP_001393731.1:p.Phe10Ile
NP_001393732.1:p.Phe10Ile
NP_001393737.1:p.Phe10Ile
NP_001393738.1:p.Phe10Ile
NP_001393742.1:p.Phe10Ile
NP_001393746.1:p.Phe10Ile
NP_001394291.1:p.Phe10Ile
LRG_219t1:c.28T>A
LRG_219:g.5115T>A
LRG_219p1:p.Phe10Ile
NC_000002.11:g.48010400T>A
NM_000179.2:c.28T>A
NR_176256.1:n.117T>A
NR_176257.1:n.117T>A
NR_176258.1:n.117T>A
NR_176259.1:n.117T>A
NR_176260.1:n.117T>A
NR_176261.1:n.117T>A

Protein change:

F10I

Molecular consequence:

NM_001281493.2:c.-709T>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001406799.1:c.-301T>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001406804.1:c.-28T>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001406807.1:c.-901T>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001406811.1:c.-709T>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001406812.1:c.-556T>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001406814.1:c.-967T>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001406816.1:c.-512T>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001406797.1:c.-38+30T>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001406801.1:c.-38+30T>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001406805.1:c.-38+30T>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001406806.1:c.-69+30T>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001406815.1:c.-280+30T>A - intron variant - [Sequence Ontology: SO:0001627]
NM_000179.3:c.28T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001281492.2:c.28T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406795.1:c.28T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406796.1:c.28T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406798.1:c.28T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406800.1:c.28T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406802.1:c.28T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406803.1:c.28T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406808.1:c.28T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406809.1:c.28T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406813.1:c.28T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406817.1:c.28T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407362.1:c.28T>A - missense variant - [Sequence Ontology: SO:0001583]
NR_176256.1:n.117T>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176257.1:n.117T>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176258.1:n.117T>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176259.1:n.117T>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176261.1:n.117T>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

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

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hypothetical protein, partial [Symplecis bicingulata]
hypothetical protein, partial [Symplecis bicingulata]
gi|1955912202|gb|QQO98872.1|

Protein
PREDICTED: Homo sapiens fibronectin type III and SPRY domain containing 2 (FSD2)...
PREDICTED: Homo sapiens fibronectin type III and SPRY domain containing 2 (FSD2), transcript variant X4, mRNA
gi|2217300130|ref|XM_011521235.4|

Nucleotide
Kidins220 kinase D-interacting substrate 220 [Rattus norvegicus]
Kidins220 kinase D-interacting substrate 220 [Rattus norvegicus]
Gene ID:116478

Gene
116478[uid] AND (alive[prop]) (1)
Gene
Gripap1 GRIP1 associated protein 1 [Rattus norvegicus]
Gripap1 GRIP1 associated protein 1 [Rattus norvegicus]
Gene ID:116493

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004006247	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (May 3, 2023)	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

SCV004006247

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(May 3, 2023)

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

WWP1 Gain-of-Function Inactivation of PTEN in Cancer Predisposition.

Lee YR, Yehia L, Kishikawa T, Ni Y, Leach B, Zhang J, Panch N, Liu J, Wei W, Eng C, Pandolfi PP.

N Engl J Med. 2020 May 28;382(22):2103-2116. doi: 10.1056/NEJMoa1914919.

PubMed [citation]

PMID:: 32459922
PMCID:: PMC7839065

Details of each submission

From Ambry Genetics, SCV004006247.2

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

Description

The p.F10I variant (also known as c.28T>A), located in coding exon 1 of the MSH6 gene, results from a T to A substitution at nucleotide position 28. The phenylalanine at codon 10 is replaced by isoleucine, an amino acid with highly similar properties. This alteration was observed once in the control ExAC (non-TCGA) dataset in a study of PTEN-negative patients who met at least the relaxed diagnostic criteria of the International Cowden Consortium (Lee YR et al. N Engl J Med, 2020 May;382:2103-2116). This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. 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

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