NM_182961.4(SYNE1):c.25359G>A (p.Trp8453Ter) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 16, 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:: RCV002996386.2

Allele description [Variation Report for NM_182961.4(SYNE1):c.25359G>A (p.Trp8453Ter)]

NM_182961.4(SYNE1):c.25359G>A (p.Trp8453Ter)

Gene:

SYNE1:spectrin repeat containing nuclear envelope protein 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

6q25.2

Genomic location:

Preferred name:

NM_182961.4(SYNE1):c.25359G>A (p.Trp8453Ter)

HGVS:

NC_000006.12:g.152140049C>T
NG_012855.2:g.502351G>A
NM_001347701.2:c.1965G>A
NM_001347702.2:c.1893G>A
NM_033071.5:c.25215G>A
NM_182961.4:c.25359G>AMANE SELECT
NP_001334630.1:p.Trp655Ter
NP_001334631.1:p.Trp631Ter
NP_149062.1:p.Trp8405Ter
NP_149062.2:p.Trp8405Ter
NP_892006.3:p.Trp8453Ter
LRG_427t1:c.25359G>A
LRG_427t2:c.25215G>A
LRG_427:g.502351G>A
LRG_427p1:p.Trp8453Ter
LRG_427p2:p.Trp8405Ter
NC_000006.11:g.152461184C>T
NM_033071.3:c.25215G>A

Protein change:

W631*

Molecular consequence:

NM_001347701.2:c.1965G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001347702.2:c.1893G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_033071.5:c.25215G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_182961.4:c.25359G>A - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Autosomal recessive ataxia, Beauce type
Synonyms:: ATAXIA, RECESSIVE, OF BEAUCE; Spinocerebellar ataxia, autosomal recessive 8; SYNE1-Related Autosomal Recessive Cerebellar Ataxia
Identifiers:: MONDO: MONDO:0012549; MedGen: C1853116; Orphanet: 88644; OMIM: 610743

Name:: Emery-Dreifuss muscular dystrophy 4, autosomal dominant (EDMD4)
Synonyms:: EMERY-DREIFUSS MUSCULAR DYSTROPHY 4 WITH VARIABLE FEATURES
Identifiers:: MONDO: MONDO:0013071; MedGen: C2751807; Orphanet: 261; OMIM: 612998

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003301532	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 16, 2022)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 19542096, 24319099, 27086870, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003301532

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 16, 2022)

germline

clinical testing

PubMed (4)
[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

Mutation of SYNE-1, encoding an essential component of the nuclear lamina, is responsible for autosomal recessive arthrogryposis.

Attali R, Warwar N, Israel A, Gurt I, McNally E, Puckelwartz M, Glick B, Nevo Y, Ben-Neriah Z, Melki J.

Hum Mol Genet. 2009 Sep 15;18(18):3462-9. doi: 10.1093/hmg/ddp290. Epub 2009 Jun 19.

PubMed [citation]

PMID:: 19542096

Mutations in CNTNAP1 and ADCY6 are responsible for severe arthrogryposis multiplex congenita with axoglial defects.

Laquérriere A, Maluenda J, Camus A, Fontenas L, Dieterich K, Nolent F, Zhou J, Monnier N, Latour P, Gentil D, Héron D, Desguerres I, Landrieu P, Beneteau C, Delaporte B, Bellesme C, Baumann C, Capri Y, Goldenberg A, Lyonnet S, Bonneau D, Estournet B, et al.

Hum Mol Genet. 2014 May 1;23(9):2279-89. doi: 10.1093/hmg/ddt618. Epub 2013 Dec 6.

PubMed [citation]

PMID:: 24319099

See all PubMed Citations (4)

Details of each submission

From Invitae, SCV003301532.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with SYNE1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Trp8405*) in the SYNE1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SYNE1 are known to be pathogenic (PMID: 19542096, 24319099, 27086870).

#	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: Feb 28, 2024

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