NM_000535.7(PMS2):c.2006+6G>A AND Lynch syndrome 4

Germline classification:: Benign (4 submissions)
Last evaluated:: Apr 5, 2023
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:: RCV000625384.15

Allele description [Variation Report for NM_000535.7(PMS2):c.2006+6G>A]

NM_000535.7(PMS2):c.2006+6G>A

Gene:

PMS2:PMS1 homolog 2, mismatch repair system component [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

7p22.1

Genomic location:

Preferred name:

NM_000535.7(PMS2):c.2006+6G>A

HGVS:

NC_000007.14:g.5986753C>T
NG_008466.1:g.27354G>A
NM_000535.7:c.2006+6G>AMANE SELECT
NM_001322003.2:c.1601+6G>A
NM_001322004.2:c.1601+6G>A
NM_001322005.2:c.1601+6G>A
NM_001322006.2:c.1850+6G>A
NM_001322007.2:c.1688+6G>A
NM_001322008.2:c.1688+6G>A
NM_001322009.2:c.1601+6G>A
NM_001322010.2:c.1445+6G>A
NM_001322011.2:c.1073+6G>A
NM_001322012.2:c.1073+6G>A
NM_001322013.2:c.1433+6G>A
NM_001322014.2:c.2006+6G>A
NM_001322015.2:c.1697+6G>A
LRG_161t1:c.2006+6G>A
LRG_161:g.27354G>A
NC_000007.13:g.6026384C>T
NM_000535.5:c.2006+6G>A
NM_000535.6:c.2006+6G>A

Links:

dbSNP: rs111905775

NCBI 1000 Genomes Browser:

rs111905775

Molecular consequence:

NM_000535.7:c.2006+6G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001322003.2:c.1601+6G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001322004.2:c.1601+6G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001322005.2:c.1601+6G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001322006.2:c.1850+6G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001322007.2:c.1688+6G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001322008.2:c.1688+6G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001322009.2:c.1601+6G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001322010.2:c.1445+6G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001322011.2:c.1073+6G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001322012.2:c.1073+6G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001322013.2:c.1433+6G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001322014.2:c.2006+6G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001322015.2:c.1697+6G>A - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Name:: Lynch syndrome 4 (LYNCH4)
Synonyms:: Colorectal cancer, hereditary nonpolyposis, type 4; Hereditary non-polyposis colorectal cancer, type 4
Identifiers:: MONDO: MONDO:0013699; MedGen: C1838333; Orphanet: 144; OMIM: 614337

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
SCV000469720	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	Benign (Jan 13, 2018)	germline	clinical testing	Citation Link,
SCV000745187	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center - VKGL Data-share Consensus	criteria provided, single submitter (ACGS Guidelines, 2013)	Benign (May 31, 2017)	germline	clinical testing	Citation Link,
SCV000785289	Counsyl	criteria provided, single submitter (Counsyl Autosomal Dominant Disease Classification criteria (2015))	Benign (Jul 7, 2017)	unknown	clinical testing	Counsyl_Autosomal_Dominant_Disease_Classification_criteria_(2015)_v1.pdf, Citation Link,
SCV004019869	Myriad Genetics, Inc.	criteria provided, single submitter (Myriad Autosomal Dominant, Autosomal Recessive and X-Linked Classification Criteria (2023))	Benign (Apr 5, 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
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Details of each submission

From Illumina Laboratory Services, Illumina, SCV000469720.3

#	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 in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.

#	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 Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center - VKGL Data-share Consensus, SCV000745187.1

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

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

From Counsyl, SCV000785289.2

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

#	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 Myriad Genetics, Inc., SCV004019869.1

#	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 intronic and is not expected to impact mRNA splicing. This variant has been observed at a population frequency that is significantly greater than expected given the associated disease prevalence and penetrance.

#	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: Oct 13, 2024

ClinVar

Relating variation to medicine