NM_001330260.2(SCN8A):c.825del (p.Asn276fs) AND Cognitive impairment with or without cerebellar ataxia

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 3, 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:: RCV001808931.2

Allele description [Variation Report for NM_001330260.2(SCN8A):c.825del (p.Asn276fs)]

NM_001330260.2(SCN8A):c.825del (p.Asn276fs)

Gene:

SCN8A:sodium voltage-gated channel alpha subunit 8 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

12q13.13

Genomic location:

Preferred name:

NM_001330260.2(SCN8A):c.825del (p.Asn276fs)

HGVS:

NC_000012.12:g.51699688del
NG_021180.3:g.114731del
NM_001177984.3:c.825del
NM_001330260.2:c.825delMANE SELECT
NM_001369788.1:c.825del
NM_014191.4:c.825del
NP_001171455.1:p.Asn276fs
NP_001317189.1:p.Asn276fs
NP_001356717.1:p.Asn276fs
NP_055006.1:p.Asn276fs
LRG_1389t1:c.825del
LRG_1389t2:c.825del
LRG_1389:g.114731del
LRG_1389p1:p.Asn276fs
LRG_1389p2:p.Asn276fs
NC_000012.11:g.52093472del

Protein change:

N276fs

Links:

dbSNP: rs2138735784

NCBI 1000 Genomes Browser:

rs2138735784

Molecular consequence:

NM_001177984.3:c.825del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001330260.2:c.825del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001369788.1:c.825del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_014191.4:c.825del - frameshift variant - [Sequence Ontology: SO:0001589]

Observations:

Condition(s)

Name:: Cognitive impairment with or without cerebellar ataxia (CIAT)
Identifiers:: MONDO: MONDO:0013680; MedGen: C3280415; OMIM: 614306

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002059201	3billion	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Jan 3, 2022)	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

SCV002059201

3billion

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Jan 3, 2022)

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	yes	1	not provided	not provided	1	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From 3billion, SCV002059201.2

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

Description

Frameshift: predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant. It is not observed in the gnomAD v2.1.1 database. However, the contribution of loss of function variants in SCN8A to Cognitive impairment with or without cerebellar ataxia is incompletely understood. Therefore, this variant is classified as uncertain significance according to the recommendation of ACMG/AMP guideline.

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

Last Updated: Dec 24, 2023

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