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NM_001005373.4(LRSAM1):c.2046G>A (p.Glu682=) AND Charcot-Marie-Tooth disease axonal type 2P

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Feb 27, 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:
RCV001215496.5

Allele description [Variation Report for NM_001005373.4(LRSAM1):c.2046G>A (p.Glu682=)]

NM_001005373.4(LRSAM1):c.2046G>A (p.Glu682=)

Gene:
LRSAM1:leucine rich repeat and sterile alpha motif containing 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
9q34.11
Genomic location:
Preferred name:
NM_001005373.4(LRSAM1):c.2046G>A (p.Glu682=)
HGVS:
  • NC_000009.12:g.127501143G>A
  • NG_032008.1:g.54658G>A
  • NM_001005373.4:c.2046G>AMANE SELECT
  • NM_001005374.4:c.2046G>A
  • NM_001190723.3:c.1965G>A
  • NM_001384142.1:c.2046G>A
  • NM_001384143.1:c.1947G>A
  • NM_001384144.1:c.1257G>A
  • NM_138361.5:c.2046G>A
  • NP_001005373.1:p.Glu682=
  • NP_001005374.1:p.Glu682=
  • NP_001177652.1:p.Glu655=
  • NP_001371071.1:p.Glu682=
  • NP_001371072.1:p.Glu649=
  • NP_001371073.1:p.Glu419=
  • NP_612370.3:p.Glu682=
  • LRG_373t1:c.2046G>A
  • LRG_373:g.54658G>A
  • LRG_373p1:p.Glu682=
  • NC_000009.11:g.130263422G>A
  • NR_168891.1:n.2575G>A
  • NR_168892.1:n.2399G>A
Links:
dbSNP: rs767249563
NCBI 1000 Genomes Browser:
rs767249563
Molecular consequence:
  • NR_168891.1:n.2575G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_168892.1:n.2399G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NM_001005373.4:c.2046G>A - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001005374.4:c.2046G>A - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001190723.3:c.1965G>A - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001384142.1:c.2046G>A - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001384143.1:c.1947G>A - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001384144.1:c.1257G>A - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_138361.5:c.2046G>A - synonymous variant - [Sequence Ontology: SO:0001819]

Condition(s)

Name:
Charcot-Marie-Tooth disease axonal type 2P
Synonyms:
CHARCOT-MARIE-TOOTH NEUROPATHY, TYPE 2P; Charcot-Marie-Tooth disease type 2P; CHARCOT-MARIE-TOOTH DISEASE, AXONAL, TYPE 2G; See all synonyms [MedGen]
Identifiers:
Gene: 431712; MONDO: MONDO:0013753; MedGen: C3280797; Orphanet: 300319; Orphanet: 99941; OMIM: 614436

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001387244Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Feb 27, 2022) 		germlineclinical testing

PubMed (3)
[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

Aberrant 5' splice sites in human disease genes: mutation pattern, nucleotide structure and comparison of computational tools that predict their utilization.

Buratti E, Chivers M, Královicová J, Romano M, Baralle M, Krainer AR, Vorechovsky I.

Nucleic Acids Res. 2007;35(13):4250-63. Epub 2007 Jun 18.

PubMed [citation]
PMID:
17576681
PMCID:
PMC1934990

Statistical features of human exons and their flanking regions.

Zhang MQ.

Hum Mol Genet. 1998 May;7(5):919-32.

PubMed [citation]
PMID:
9536098
See all PubMed Citations (3)

Details of each submission

From Invitae, SCV001387244.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

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. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. ClinVar contains an entry for this variant (Variation ID: 944977). This variant has not been reported in the literature in individuals affected with LRSAM1-related conditions. This variant is present in population databases (rs767249563, gnomAD 0.02%). This sequence change affects codon 682 of the LRSAM1 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the LRSAM1 protein. This variant also falls at the last nucleotide of exon 24, which is part of the consensus splice site for this exon.

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

Last Updated: Feb 14, 2024