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

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 [Variation Report for NM_002468.5(MYD88):c.755T>C (p.Leu252Pro)]

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:
1

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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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV004020299Wasik Lab, Fox Chase Cancer Center
no assertion criteria provided
Likely pathogenic
(Jul 25, 2023)
somaticclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedsomaticyes1not providednot providednot providednot providedclinical 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

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
11not providednot providedclinical 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.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1somaticyesnot providednot providednot provided1not providednot providednot provided

Last Updated: May 12, 2024