NM_000251.3(MSH2):c.198C>T (p.Tyr66=) AND Lynch syndrome 1

Germline classification:: Conflicting interpretations of pathogenicity (3 submissions)
Last evaluated:: Mar 20, 2023
Review status:: criteria provided, conflicting classifications

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:: RCV000409186.11

Allele description [Variation Report for NM_000251.3(MSH2):c.198C>T (p.Tyr66=)]

NM_000251.3(MSH2):c.198C>T (p.Tyr66=)

Gene:

MSH2:mutS homolog 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2p21

Genomic location:

Preferred name:

NM_000251.3(MSH2):c.198C>T (p.Tyr66=)

Other names:

p.Y66Y:TAC>TAT

HGVS:

NC_000002.12:g.47403389C>T
NG_007110.2:g.5266C>T
NG_095167.1:g.593C>T
NM_000251.3:c.198C>TMANE SELECT
NM_001258281.1:c.-1C>T
NM_001406631.1:c.198C>T
NM_001406632.1:c.198C>T
NM_001406633.1:c.198C>T
NM_001406634.1:c.198C>T
NM_001406635.1:c.198C>T
NM_001406636.1:c.198C>T
NM_001406637.1:c.198C>T
NM_001406638.1:c.198C>T
NM_001406639.1:c.198C>T
NM_001406640.1:c.198C>T
NM_001406641.1:c.198C>T
NM_001406642.1:c.198C>T
NM_001406643.1:c.198C>T
NM_001406644.1:c.198C>T
NM_001406645.1:c.198C>T
NM_001406646.1:c.198C>T
NM_001406647.1:c.198C>T
NM_001406648.1:c.198C>T
NM_001406649.1:c.198C>T
NM_001406650.1:c.198C>T
NM_001406651.1:c.198C>T
NM_001406652.1:c.198C>T
NM_001406653.1:c.198C>T
NM_001406654.1:c.-143C>T
NM_001406655.1:c.198C>T
NM_001406656.1:c.-798C>T
NM_001406657.1:c.198C>T
NM_001406658.1:c.-1121C>T
NM_001406659.1:c.-1271C>T
NM_001406660.1:c.-1468C>T
NM_001406661.1:c.-1423C>T
NM_001406662.1:c.-1340C>T
NM_001406666.1:c.198C>T
NM_001406669.1:c.-1271C>T
NM_001406672.1:c.198C>T
NM_001406674.1:c.198C>T
NP_000242.1:p.Tyr66=
NP_000242.1:p.Tyr66=
NP_001393560.1:p.Tyr66=
NP_001393561.1:p.Tyr66=
NP_001393562.1:p.Tyr66=
NP_001393563.1:p.Tyr66=
NP_001393564.1:p.Tyr66=
NP_001393565.1:p.Tyr66=
NP_001393566.1:p.Tyr66=
NP_001393567.1:p.Tyr66=
NP_001393568.1:p.Tyr66=
NP_001393569.1:p.Tyr66=
NP_001393570.1:p.Tyr66=
NP_001393571.1:p.Tyr66=
NP_001393572.1:p.Tyr66=
NP_001393573.1:p.Tyr66=
NP_001393574.1:p.Tyr66=
NP_001393575.1:p.Tyr66=
NP_001393576.1:p.Tyr66=
NP_001393577.1:p.Tyr66=
NP_001393578.1:p.Tyr66=
NP_001393579.1:p.Tyr66=
NP_001393580.1:p.Tyr66=
NP_001393581.1:p.Tyr66=
NP_001393582.1:p.Tyr66=
NP_001393584.1:p.Tyr66=
NP_001393586.1:p.Tyr66=
NP_001393595.1:p.Tyr66=
NP_001393601.1:p.Tyr66=
NP_001393603.1:p.Tyr66=
LRG_218t1:c.198C>T
LRG_218:g.5266C>T
LRG_218p1:p.Tyr66=
NC_000002.11:g.47630528C>T
NM_000251.1:c.198C>T
NM_000251.2:c.198C>T
NM_001258281.1:c.-1C>T
NR_176230.1:n.234C>T
NR_176231.1:n.234C>T
NR_176232.1:n.234C>T
NR_176233.1:n.234C>T
NR_176234.1:n.234C>T
NR_176235.1:n.234C>T
NR_176236.1:n.234C>T
NR_176237.1:n.234C>T
NR_176238.1:n.234C>T
NR_176239.1:n.234C>T
NR_176240.1:n.234C>T
NR_176241.1:n.234C>T
NR_176242.1:n.234C>T
NR_176243.1:n.234C>T
NR_176244.1:n.234C>T
NR_176245.1:n.234C>T
NR_176246.1:n.234C>T
NR_176247.1:n.234C>T
NR_176248.1:n.234C>T
NR_176249.1:n.234C>T
NR_176250.1:n.234C>T
p.Y66Y

Links:

dbSNP: rs730881784

NCBI 1000 Genomes Browser:

rs730881784

Molecular consequence:

NM_001258281.1:c.-1C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001406654.1:c.-143C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001406656.1:c.-798C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001406658.1:c.-1121C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001406659.1:c.-1271C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001406660.1:c.-1468C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001406661.1:c.-1423C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001406662.1:c.-1340C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001406669.1:c.-1271C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NR_176230.1:n.234C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176231.1:n.234C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176232.1:n.234C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176233.1:n.234C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176234.1:n.234C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176235.1:n.234C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176236.1:n.234C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176237.1:n.234C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176238.1:n.234C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176239.1:n.234C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176240.1:n.234C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176241.1:n.234C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176242.1:n.234C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176243.1:n.234C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176244.1:n.234C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176245.1:n.234C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176246.1:n.234C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176247.1:n.234C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176248.1:n.234C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176249.1:n.234C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176250.1:n.234C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_000251.3:c.198C>T - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001406631.1:c.198C>T - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001406632.1:c.198C>T - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001406633.1:c.198C>T - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001406634.1:c.198C>T - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001406635.1:c.198C>T - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001406636.1:c.198C>T - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001406637.1:c.198C>T - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001406638.1:c.198C>T - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001406639.1:c.198C>T - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001406640.1:c.198C>T - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001406641.1:c.198C>T - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001406642.1:c.198C>T - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001406643.1:c.198C>T - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001406644.1:c.198C>T - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001406645.1:c.198C>T - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001406646.1:c.198C>T - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001406647.1:c.198C>T - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001406648.1:c.198C>T - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001406649.1:c.198C>T - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001406650.1:c.198C>T - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001406651.1:c.198C>T - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001406652.1:c.198C>T - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001406653.1:c.198C>T - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001406655.1:c.198C>T - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001406657.1:c.198C>T - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001406666.1:c.198C>T - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001406672.1:c.198C>T - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001406674.1:c.198C>T - synonymous variant - [Sequence Ontology: SO:0001819]

Condition(s)

Name:: Lynch syndrome 1
Synonyms:: COLON CANCER, FAMILIAL NONPOLYPOSIS, TYPE 1; MSH2-Related Hereditary Non-Polyposis Colon Cancer; Lynch syndrome I; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0007356; MedGen: C2936783; Orphanet: 144; OMIM: 120435

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000489340	Counsyl	criteria provided, single submitter (Counsyl Autosomal Dominant Disease Classification criteria (2015))	Likely benign (Sep 20, 2016)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID] Counsyl Autosomal Dominant Disease Classification criteria (2015), Citation Link,
SCV001304221	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	Uncertain significance (Apr 27, 2017)	germline	clinical testing	Citation Link,
SCV004018293	Myriad Genetics, Inc.	criteria provided, single submitter (Myriad Autosomal Dominant, Autosomal Recessive and X-Linked Classification Criteria (2023))	Benign (Mar 20, 2023)	unknown	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000489340

Counsyl

criteria provided, single submitter

(Counsyl Autosomal Dominant Disease Classification criteria (2015))

Likely benign
(Sep 20, 2016)

unknown

clinical testing

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

Counsyl Autosomal Dominant Disease Classification criteria (2015),

Citation Link,

SCV001304221

Illumina Laboratory Services, Illumina

criteria provided, single submitter

(ICSL Variant Classification Criteria 13 December 2019)

Uncertain significance
(Apr 27, 2017)

germline

clinical testing

Citation Link,

SCV004018293

Myriad Genetics, Inc.

criteria provided, single submitter

(Myriad Autosomal Dominant, Autosomal Recessive and X-Linked Classification Criteria (2023))

Benign
(Mar 20, 2023)

unknown

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
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Frequency of mutations in mismatch repair genes in a population-based study of women with ovarian cancer.

Pal T, Akbari MR, Sun P, Lee JH, Fulp J, Thompson Z, Coppola D, Nicosia S, Sellers TA, McLaughlin J, Risch HA, Rosen B, Shaw P, Schildkraut J, Narod SA.

Br J Cancer. 2012 Nov 6;107(10):1783-90. doi: 10.1038/bjc.2012.452. Epub 2012 Oct 9.

PubMed [citation]

PMID:: 23047549
PMCID:: PMC3493867

Details of each submission

From Counsyl, SCV000489340.2

#	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	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Illumina Laboratory Services, Illumina, SCV001304221.1

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

Description

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown 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

From Myriad Genetics, Inc., SCV004018293.1

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

Description

This variant is considered benign. This variant is a silent/synonymous amino acid change and it is not expected to impact splicing.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Nov 10, 2024

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