NM_001365088.1(SLC12A6):c.1950dup (p.Leu651fs) AND Agenesis of the corpus callosum with peripheral neuropathy

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Aug 23, 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:: RCV002281814.1

Allele description [Variation Report for NM_001365088.1(SLC12A6):c.1950dup (p.Leu651fs)]

NM_001365088.1(SLC12A6):c.1950dup (p.Leu651fs)

Gene:

SLC12A6:solute carrier family 12 member 6 [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

15q14

Genomic location:

Preferred name:

NM_001365088.1(SLC12A6):c.1950dup (p.Leu651fs)

HGVS:

NC_000015.10:g.34244071dup
NG_007951.1:g.98999dup
NM_001042494.2:c.1773dup
NM_001042495.2:c.1773dup
NM_001042496.2:c.1923dup
NM_001042497.2:c.1905dup
NM_001365088.1:c.1950dupMANE SELECT
NM_005135.2:c.1797dup
NM_133647.2:c.1950dup
NP_001035959.1:p.Leu592fs
NP_001035960.1:p.Leu592fs
NP_001035961.1:p.Leu642fs
NP_001035962.1:p.Leu636fs
NP_001352017.1:p.Leu651fs
NP_005126.1:p.Leu600fs
NP_598408.1:p.Leu651Serfs
NP_598408.1:p.Leu651fs
LRG_270t1:c.1797dup
LRG_270t2:c.1945dup
LRG_270:g.98999dup
LRG_270p1:p.Leu600fs
LRG_270p2:p.Leu651Serfs
NC_000015.9:g.34536266_34536267insA
NC_000015.9:g.34536272dup
NM_133647.1:c.1945dup
NM_133647.1:c.1950dupT

Protein change:

L592fs

Molecular consequence:

NM_001042494.2:c.1773dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001042495.2:c.1773dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001042496.2:c.1923dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001042497.2:c.1905dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001365088.1:c.1950dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_005135.2:c.1797dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_133647.2:c.1950dup - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Agenesis of the corpus callosum with peripheral neuropathy (ACCPN)
Synonyms:: Andermann syndrome; Charlevoix disease; Corpus callosum agenesis neuronopathy; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0000902; MedGen: C0795950; Orphanet: 1496; OMIM: 218000

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002572280	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Likely pathogenic (Aug 23, 2022)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002572280

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Likely pathogenic
(Aug 23, 2022)

germline

clinical testing

Citation Link

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

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV002572280.1

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

Description

Variant summary: SLC12A6 c.1950dupT (p.Leu651SerfsX68) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory and also observed in the HGMD database. The variant was absent in 251226 control chromosomes. To our knowledge, no occurrence of c.1950dupT in individuals affected with Andermann Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic.

#	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: Oct 26, 2024

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