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NC_000016.9:g.(?_70310369)_(70311077_?)dup AND Charcot-Marie-Tooth disease type 2

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Apr 15, 2023
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:
RCV004582800.2

Allele description [Variation Report for NC_000016.9:g.(?_70310369)_(70311077_?)dup]

NC_000016.9:g.(?_70310369)_(70311077_?)dup

Gene:
AARS1:alanyl-tRNA synthetase 1 [Gene - OMIM - HGNC]
Variant type:
Duplication
Cytogenetic location:
16q22.1
Genomic location:
Chr16: 70310369 - 70311077 (on Assembly GRCh37)
Preferred name:
NC_000016.9:g.(?_70310369)_(70311077_?)dup
HGVS:
NC_000016.9:g.(?_70310369)_(70311077_?)dup

Condition(s)

Name:
Charcot-Marie-Tooth disease type 2
Synonyms:
Charcot-Marie-Tooth, Type 2
Identifiers:
MONDO: MONDO:0018993; MedGen: C0270914

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV005062390Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Likely pathogenic
(Apr 15, 2023) 		unknownclinical testing

PubMed (5)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

Next-generation sequencing of duplication CNVs reveals that most are tandem and some create fusion genes at breakpoints.

Newman S, Hermetz KE, Weckselblatt B, Rudd MK.

Am J Hum Genet. 2015 Feb 5;96(2):208-20. doi: 10.1016/j.ajhg.2014.12.017. Epub 2015 Jan 29.

PubMed [citation]
PMID:
25640679
PMCID:
PMC4320257

Loss-of-function alanyl-tRNA synthetase mutations cause an autosomal-recessive early-onset epileptic encephalopathy with persistent myelination defect.

Simons C, Griffin LB, Helman G, Golas G, Pizzino A, Bloom M, Murphy JL, Crawford J, Evans SH, Topper S, Whitehead MT, Schreiber JM, Chapman KA, Tifft C, Lu KB, Gamper H, Shigematsu M, Taft RJ, Antonellis A, Hou YM, Vanderver A.

Am J Hum Genet. 2015 Apr 2;96(4):675-81. doi: 10.1016/j.ajhg.2015.02.012. Epub 2015 Mar 26.

PubMed [citation]
PMID:
25817015
PMCID:
PMC4385183
See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV005062390.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant has not been reported in the literature in individuals affected with AARS-related conditions. This variant results in a copy number gain of the genomic region encompassing exon(s) 3-4 of the AARS gene. While the exact position of this variant cannot be determined from the data, sub-genic copy number gains are generally in tandem (PMID: 25640679). This variant is predicted to be out-of-frame, and may result in an absent or disrupted protein product. Loss-of-function variants in AARS are known to be pathogenic (PMID: 25817015, 28493438, 34446925).

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

Last Updated: Sep 29, 2024