NM_002468.5(MYD88):c.755T>C (p.Leu252Pro) AND Malignant lymphoma, large B-cell, diffuse

This record was updated by the submitter. Please see the current version.

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Jul 25, 2023
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

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:: RCV003315524.2

Allele description

NM_002468.5(MYD88):c.755T>C (p.Leu252Pro)

Gene:

MYD88:MYD88 innate immune signal transduction adaptor [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

3p22.2

Genomic location:

Preferred name:

NM_002468.5(MYD88):c.755T>C (p.Leu252Pro)

Other names:

L265P; *160R; *192R; *246R; *147R; *201R

HGVS:

NC_000003.12:g.38141150T>C
NG_016964.1:g.7673T>C
NG_023225.1:g.1093A>G
NM_001172566.2:c.439T>C
NM_001172567.2:c.779T>C
NM_001172568.2:c.620T>C
NM_001172569.3:c.574T>C
NM_001365876.1:c.736T>C
NM_001365877.1:c.601T>C
NM_001374787.1:c.712T>C
NM_002468.5:c.755T>CMANE SELECT
NP_001166037.2:p.Ter147Arg
NP_001166038.2:p.Leu260Pro
NP_001166039.2:p.Leu207Pro
NP_001166040.2:p.Ter192Arg
NP_001352805.1:p.Ter246Arg
NP_001352806.1:p.Ter201Arg
NP_001361716.1:p.Ter238Arg
NP_002459.3:p.Leu252Pro
LRG_157:g.7673T>C
NC_000003.11:g.38182641T>C
NM_002468.4:c.794T>C

Note:

Note that rs38182641, from OMIM 602170.0004, is incorrect.

Protein change:

L207P; LEU265PRO

Links:

OMIM: 602170.0004; dbSNP: rs387907272

NCBI 1000 Genomes Browser:

rs387907272

Molecular consequence:

NM_001172567.2:c.779T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001172568.2:c.620T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_002468.5:c.755T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001172566.2:c.439T>C - stop lost - [Sequence Ontology: SO:0001578]
NM_001172569.3:c.574T>C - stop lost - [Sequence Ontology: SO:0001578]
NM_001365876.1:c.736T>C - stop lost - [Sequence Ontology: SO:0001578]
NM_001365877.1:c.601T>C - stop lost - [Sequence Ontology: SO:0001578]
NM_001374787.1:c.712T>C - stop lost - [Sequence Ontology: SO:0001578]

Observations:

Condition(s)

Name:: Malignant lymphoma, large B-cell, diffuse
Synonyms:: Diffuse large B cell lymphoma
Identifiers:: MONDO: MONDO:0018905; MeSH: D016403; MedGen: C0079744

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004020299	Wasik Lab, Fox Chase Cancer Center	no assertion criteria provided	Likely pathogenic (Jul 25, 2023)	somatic	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

SCV004020299

Wasik Lab, Fox Chase Cancer Center

no assertion criteria provided

Likely pathogenic
(Jul 25, 2023)

somatic

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	somatic	yes	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Oncogenically active MYD88 mutations in human lymphoma.

Ngo VN, Young RM, Schmitz R, Jhavar S, Xiao W, Lim KH, Kohlhammer H, Xu W, Yang Y, Zhao H, Shaffer AL, Romesser P, Wright G, Powell J, Rosenwald A, Muller-Hermelink HK, Ott G, Gascoyne RD, Connors JM, Rimsza LM, Campo E, Jaffe ES, et al.

Nature. 2011 Feb 3;470(7332):115-9. doi: 10.1038/nature09671. Epub 2010 Dec 22.

PubMed [citation]

PMID:: 21179087
PMCID:: PMC5024568

Details of each submission

From Wasik Lab, Fox Chase Cancer Center, SCV004020299.1

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

Description

Peripheral blood containing DLBCL collected for sequencing at initial diagnosis August 2018. Tumor tissue sequenced at recurrence September 2019.

Description

This variant was observed in a patient with DLBCL that presented in leukemic form, best classified as MCD/C5 DLBCL, an ABC subtype. Despite an initial good clinical response to BTK inhibitor ibrutinib, anti-CD20 antibody rituxan, alkylating agent bendamustine, and hematopoietic stem-cell transplant, the lymphoma relapsed, accompanied by morphologic and molecular evidence of disease progression. MYD88 L265P was detected in the tumor at presentation and with increased variant allele frequency, genomic copy number, and RNA expression at recurrence. MYD88 is an essential signaling adaptor protein that interacts with Toll-like receptors (TLR), kinases IRAK1 and IRAK4 to form a ‘myddosome complex’. The L265P mutation is a gain of function oncogenic mutation resulting in spontaneous assembly of the myddosome complex (Ngo et al. 2011) and ultimately NF-kB pathway activation.

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

Last Updated: May 12, 2024

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