NM_170707.4(LMNA):c.1812_1823del (p.Ala605_Gly608del) AND Charcot-Marie-Tooth disease type 2

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Mar 13, 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:: RCV003743497.2

Allele description [Variation Report for NM_170707.4(LMNA):c.1812_1823del (p.Ala605_Gly608del)]

NM_170707.4(LMNA):c.1812_1823del (p.Ala605_Gly608del)

Gene:

LMNA:lamin A/C [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

1q22

Genomic location:

Preferred name:

NM_170707.4(LMNA):c.1812_1823del (p.Ala605_Gly608del)

HGVS:

NC_000001.11:g.156138601_156138612del
NG_008692.2:g.61029_61040del
NM_001257374.3:c.1476_1487del
NM_001282626.2:c.1812_1818+5del
NM_001406983.1:c.1812_1823del
NM_001406985.1:c.1812_1823del
NM_001406986.1:c.1569_1580del
NM_001406987.1:c.1569_1580del
NM_001406988.1:c.1515_1526del
NM_001406989.1:c.1476_1487del
NM_001406990.1:c.1254_1265del
NM_001406991.1:c.1812_1823del
NM_001406993.1:c.1254_1265del
NM_001406994.1:c.1188_1199del
NM_001406995.1:c.1254_1265del
NM_001406996.1:c.1254_1265del
NM_001406997.1:c.1254_1265del
NM_001406999.1:c.1188_1199del
NM_001407000.1:c.1188_1199del
NM_001407001.1:c.1188_1199del
NM_170707.4:c.1812_1823delMANE SELECT
NM_170708.4:c.1722_1733del
NP_001244303.1:p.Ala493_Gly496del
NP_001393912.1:p.Ala605_Gly608del
NP_001393914.1:p.Ala605_Gly608del
NP_001393915.1:p.Ala524_Gly527del
NP_001393916.1:p.Ala524_Gly527del
NP_001393917.1:p.Ala506_Gly509del
NP_001393918.1:p.Ala493_Gly496del
NP_001393919.1:p.Ala419_Gly422del
NP_001393920.1:p.Ala605_Gly608del
NP_001393922.1:p.Ala419_Gly422del
NP_001393923.1:p.Ala397_Gly400del
NP_001393924.1:p.Ala419_Gly422del
NP_001393925.1:p.Ala419_Gly422del
NP_001393926.1:p.Ala419_Gly422del
NP_001393928.1:p.Ala397_Gly400del
NP_001393929.1:p.Ala397_Gly400del
NP_001393930.1:p.Ala397_Gly400del
NP_733821.1:p.Ala605_Gly608del
NP_733821.1:p.Ala605_Gly608del
NP_733822.1:p.Ala575_Gly578del
NP_733822.1:p.Ala575_Gly578del
LRG_254t2:c.1812_1823del
LRG_254t3:c.1722_1733del
LRG_254:g.61029_61040del
LRG_254p2:p.Ala605_Gly608del
LRG_254p3:p.Ala575_Gly578del
NC_000001.10:g.156108390_156108401del
NC_000001.10:g.156108392_156108403del
NM_170707.2:c.1812_1823delAGCCCAGGTGGG
NM_170708.2:c.1722_1733delAGCCCAGGTGGG

Molecular consequence:

NM_001257374.3:c.1476_1487del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001406983.1:c.1812_1823del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001406985.1:c.1812_1823del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001406986.1:c.1569_1580del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001406987.1:c.1569_1580del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001406988.1:c.1515_1526del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001406989.1:c.1476_1487del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001406990.1:c.1254_1265del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001406991.1:c.1812_1823del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001406993.1:c.1254_1265del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001406994.1:c.1188_1199del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001406995.1:c.1254_1265del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001406996.1:c.1254_1265del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001406997.1:c.1254_1265del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001406999.1:c.1188_1199del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001407000.1:c.1188_1199del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001407001.1:c.1188_1199del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_170707.4:c.1812_1823del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_170708.4:c.1722_1733del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001282626.2:c.1812_1818+5del - splice donor variant - [Sequence Ontology: SO:0001575]

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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ninein isoform X22 [Homo sapiens]
ninein isoform X22 [Homo sapiens]
gi|2462540514|ref|XP_054232167.1|

Protein
Scyphophorus acupunctatus cytochrome oxidase subunit I (COI) gene, partial cds; ...
Scyphophorus acupunctatus cytochrome oxidase subunit I (COI) gene, partial cds; mitochondrial.
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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004519571	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Mar 13, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004519571

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Mar 13, 2023)

germline

clinical testing

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

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

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, SCV004519571.1

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

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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This variant has not been reported in the literature in individuals affected with LMNA-related conditions. This variant is present in population databases (rs762745643, gnomAD 0.003%). This variant, c.1812_1823del, results in the deletion of 4 amino acid(s) of the LMNA protein (p.Ala605_Gly608del), but otherwise preserves the integrity of the reading frame.

#	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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