NM_000249.4(MLH1):c.155_156del (p.Lys52fs) AND Colorectal cancer, hereditary nonpolyposis, type 2

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Jul 11, 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:: RCV003453263.2

Allele description [Variation Report for NM_000249.4(MLH1):c.155_156del (p.Lys52fs)]

NM_000249.4(MLH1):c.155_156del (p.Lys52fs)

Gene:

MLH1:mutL homolog 1 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

3p22.2

Genomic location:

Preferred name:

NM_000249.4(MLH1):c.155_156del (p.Lys52fs)

HGVS:

NC_000003.12:g.36996657_36996658del
NG_007109.2:g.8308_8309del
NG_008418.1:g.1648_1649del
NM_000249.4:c.155_156delMANE SELECT
NM_001167617.3:c.-135_-134del
NM_001167618.3:c.-569_-568del
NM_001167619.3:c.-477_-476del
NM_001258271.2:c.155_156del
NM_001258273.2:c.-517+2994_-517+2995del
NM_001258274.3:c.-714_-713del
NM_001354615.2:c.-472_-471del
NM_001354616.2:c.-477_-476del
NM_001354617.2:c.-569_-568del
NM_001354618.2:c.-569_-568del
NM_001354619.2:c.-569_-568del
NM_001354620.2:c.-135_-134del
NM_001354621.2:c.-662_-661del
NM_001354622.2:c.-775_-774del
NM_001354623.2:c.-723+2767_-723+2768del
NM_001354624.2:c.-672_-671del
NM_001354625.2:c.-575_-574del
NM_001354626.2:c.-672_-671del
NM_001354627.2:c.-672_-671del
NM_001354628.2:c.155_156del
NM_001354629.2:c.155_156del
NM_001354630.2:c.155_156del
NP_000240.1:p.Lys52fs
NP_001245200.1:p.Lys52fs
NP_001341557.1:p.Lys52fs
NP_001341558.1:p.Lys52fs
NP_001341559.1:p.Lys52fs
LRG_216:g.8308_8309del
NC_000003.11:g.37038148_37038149del
NM_000249.3:c.155_156delAA
p.K52RfsX26

Protein change:

K52fs

Links:

dbSNP: rs63750028

NCBI 1000 Genomes Browser:

rs63750028

Molecular consequence:

NM_001167617.3:c.-135_-134del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001167618.3:c.-569_-568del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001167619.3:c.-477_-476del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001258274.3:c.-714_-713del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354615.2:c.-472_-471del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354616.2:c.-477_-476del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354617.2:c.-569_-568del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354618.2:c.-569_-568del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354619.2:c.-569_-568del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354620.2:c.-135_-134del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354621.2:c.-662_-661del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354622.2:c.-775_-774del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354624.2:c.-672_-671del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354625.2:c.-575_-574del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354626.2:c.-672_-671del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354627.2:c.-672_-671del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_000249.4:c.155_156del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001258271.2:c.155_156del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354628.2:c.155_156del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354629.2:c.155_156del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354630.2:c.155_156del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001258273.2:c.-517+2994_-517+2995del - intron variant - [Sequence Ontology: SO:0001627]
NM_001354623.2:c.-723+2767_-723+2768del - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Name:: Colorectal cancer, hereditary nonpolyposis, type 2 (LYNCH2)
Synonyms:: COLON CANCER, FAMILIAL NONPOLYPOSIS, TYPE 2; Lynch syndrome II; MLH1-Related Lynch Syndrome; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0012249; MedGen: C1333991; Orphanet: 144; OMIM: 609310

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004186334	Myriad Genetics, Inc.	criteria provided, single submitter (Myriad Autosomal Dominant, Autosomal Recessive and X-Linked Classification Criteria (2023))	Pathogenic (Jul 11, 2023)	unknown	clinical testing	Citation Link,
SCV004193069	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jul 29, 2021)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004186334

Myriad Genetics, Inc.

criteria provided, single submitter

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

Pathogenic
(Jul 11, 2023)

unknown

clinical testing

Citation Link,

SCV004193069

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Jul 29, 2021)

unknown

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	unknown	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

Details of each submission

From Myriad Genetics, Inc., SCV004186334.1

#	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 pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.

#	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 Baylor Genetics, SCV004193069.1

#	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

Last Updated: Dec 30, 2023

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