NM_133259.4(LRPPRC):c.3737_3740del (p.Asn1246fs) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jun 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:: RCV002922901.3

Allele description [Variation Report for NM_133259.4(LRPPRC):c.3737_3740del (p.Asn1246fs)]

NM_133259.4(LRPPRC):c.3737_3740del (p.Asn1246fs)

Gene:

LRPPRC:leucine rich pentatricopeptide repeat containing [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

2p21

Genomic location:

Preferred name:

NM_133259.4(LRPPRC):c.3737_3740del (p.Asn1246fs)

HGVS:

NC_000002.12:g.43899306_43899309del
NG_008247.1:g.101699_101702del
NM_133259.4:c.3737_3740delMANE SELECT
NP_573566.2:p.Asn1246fs
NC_000002.11:g.44126443_44126446del
NC_000002.11:g.44126445_44126448del

Protein change:

N1246fs

Molecular consequence:

NM_133259.4:c.3737_3740del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003262771	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jun 15, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 26510951, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003262771

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jun 15, 2023)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

LRPPRC mutations cause early-onset multisystem mitochondrial disease outside of the French-Canadian population.

Oláhová M, Hardy SA, Hall J, Yarham JW, Haack TB, Wilson WC, Alston CL, He L, Aznauryan E, Brown RM, Brown GK, Morris AA, Mundy H, Broomfield A, Barbosa IA, Simpson MA, Deshpande C, Moeslinger D, Koch J, Stettner GM, Bonnen PE, Prokisch H, et al.

Brain. 2015 Dec;138(Pt 12):3503-19. doi: 10.1093/brain/awv291. Epub 2015 Oct 27.

PubMed [citation]

PMID:: 26510951
PMCID:: PMC4655343

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, SCV003262771.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 2053945). This variant has not been reported in the literature in individuals affected with LRPPRC-related conditions. This variant is present in population databases (rs764402730, gnomAD 0.0009%). This sequence change creates a premature translational stop signal (p.Asn1246Serfs*58) in the LRPPRC gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in LRPPRC are known to be pathogenic (PMID: 26510951).

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

Last Updated: Sep 29, 2024

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