NM_000399.5(EGR2):c.1271_1274del (p.Lys424fs) AND Charcot-Marie-Tooth disease, type I

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Jan 17, 2022
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
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:
RCV003007856.3

Allele description [Variation Report for NM_000399.5(EGR2):c.1271_1274del (p.Lys424fs)]

NM_000399.5(EGR2):c.1271_1274del (p.Lys424fs)

Gene:
EGR2:early growth response 2 [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
10q21.3
Genomic location:
Preferred name:
NM_000399.5(EGR2):c.1271_1274del (p.Lys424fs)
HGVS:
  • NC_000010.11:g.62813367_62813370del
  • NG_008936.2:g.111534_111537del
  • NM_000399.5:c.1271_1274delMANE SELECT
  • NM_001136177.3:c.1271_1274del
  • NM_001136178.2:c.1271_1274del
  • NM_001136179.3:c.1121_1124del
  • NM_001321037.2:c.1121_1124del
  • NM_001410931.1:c.1307_1310delAGAA
  • NP_000390.2:p.Lys424Serfs
  • NP_000390.2:p.Lys424fs
  • NP_001129649.1:p.Lys424fs
  • NP_001129650.1:p.Lys424fs
  • NP_001129651.1:p.Lys374fs
  • NP_001307966.1:p.Lys374fs
  • NP_001397860.1:p.Lys437Serfs
  • LRG_239t1:c.1268_1271del
  • LRG_239:g.111534_111537del
  • LRG_239p1:p.Lys424Serfs
  • NC_000010.10:g.64573124_64573127del
  • NC_000010.10:g.64573127_64573130del
  • NM_000399.3:c.1268_1271delAGAA
Protein change:
K374fs
Molecular consequence:
  • NM_000399.5:c.1271_1274del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001136177.3:c.1271_1274del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001136178.2:c.1271_1274del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001136179.3:c.1121_1124del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001321037.2:c.1121_1124del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001410931.1:c.1307_1310delAGAA - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:
Charcot-Marie-Tooth disease, type I (CMT1)
Synonyms:
Charcot-Marie-Tooth Neuropathy Type 1; Hereditary Motor and Sensory Neuropathy 1; Charcot-Marie-Tooth, Type 1
Identifiers:
MONDO: MONDO:0019011; MedGen: C0751036

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV003304580Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Jan 17, 2022) 		germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Sequential targeted exome sequencing of 1001 patients affected by unexplained limb-girdle weakness.

Töpf A, Johnson K, Bates A, Phillips L, Chao KR, England EM, Laricchia KM, Mullen T, Valkanas E, Xu L, Bertoli M, Blain A, Casasús AB, Duff J, Mroczek M, Specht S, Lek M, Ensini M, MacArthur DG; MYO-SEQ consortium., Straub V.

Genet Med. 2020 Sep;22(9):1478-1488. doi: 10.1038/s41436-020-0840-3. Epub 2020 Jun 11.

PubMed [citation]
PMID:
32528171
PMCID:
PMC7462745

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003304580.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

This frameshift has been observed in individual(s) with clinical features of EGR2-related conditions (PMID: 32528171). This variant is not present in population databases (gnomAD no frequency). This sequence change results in a frameshift in the EGR2 gene (p.Lys424Serfs*110). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 53 amino acid(s) of the EGR2 protein and extend the protein by 56 additional amino acid residues. This variant results in an extension of the EGR2 protein. Other variant(s) that result in a similarly extended protein product (p.Ser439Leufs*96) have been observed in individuals with EGR2-related disease (Invitae). This suggests that these extensions may be clinically significant. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024