NM_173076.3(ABCA12):c.7444C>T (p.Arg2482Ter) AND Lamellar ichthyosis

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Apr 27, 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:: RCV002231097.1

Allele description [Variation Report for NM_173076.3(ABCA12):c.7444C>T (p.Arg2482Ter)]

NM_173076.3(ABCA12):c.7444C>T (p.Arg2482Ter)

Genes:

ABCA12:ATP binding cassette subfamily A member 12 [Gene - OMIM - HGNC]
SNHG31:small nucleolar RNA host gene 31 [Gene - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2q35

Genomic location:

Preferred name:

NM_173076.3(ABCA12):c.7444C>T (p.Arg2482Ter)

Other names:

p.Arg2482Ter

HGVS:

NC_000002.12:g.214937608G>A
NG_007074.1:g.205820C>T
NM_015657.4:c.6490C>T
NM_173076.3:c.7444C>TMANE SELECT
NP_056472.2:p.Arg2164Ter
NP_056472.2:p.Arg2164Ter
NP_775099.2:p.Arg2482Ter
NC_000002.11:g.215802332G>A
NM_015657.3:c.6490C>T
NM_173076.2:c.7444C>T
NR_103740.2:n.7942C>T

Protein change:

R2164*

Links:

dbSNP: rs199503269

NCBI 1000 Genomes Browser:

rs199503269

Molecular consequence:

NR_103740.2:n.7942C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_015657.4:c.6490C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_173076.3:c.7444C>T - nonsense - [Sequence Ontology: SO:0001587]

Functional consequence:

unknown functional consequence

Condition(s)

Name:: Lamellar ichthyosis
Identifiers:: MONDO: MONDO:0017778; MedGen: C5848247

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002511983	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Pathogenic (Apr 27, 2022)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 17684380, 28851938, 31586585, 26740202, 19262603 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002511983

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

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Pathogenic
(Apr 27, 2022)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

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

Citations

PubMed

Compound heterozygous ABCA12 mutations including a novel nonsense mutation underlie harlequin ichthyosis.

Akiyama M, Sakai K, Sato T, McMillan JR, Goto M, Sawamura D, Shimizu H.

Dermatology. 2007;215(2):155-9.

PubMed [citation]

PMID:: 17684380

Prevalence of Rare Genetic Variations and Their Implications in NGS-data Interpretation.

Cho Y, Lee CH, Jeong EG, Kim MH, Hong JH, Ko Y, Lee B, Yun G, Kim BJ, Jung J, Jung J, Lee JS.

Sci Rep. 2017 Aug 29;7(1):9810. doi: 10.1038/s41598-017-09247-5.

PubMed [citation]

PMID:: 28851938
PMCID:: PMC5574920

See all PubMed Citations (5)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV002511983.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

Variant summary: ABCA12 c.7444C>T (p.Arg2482X) 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. The variant allele was found at a frequency of 2e-05 in 250934 control chromosomes. c.7444C>T has been reported in the literature as a homozygous or compound heterozygous genotype in multiple individuals affected with features of Lamellar Ichthyosis/Harlequin Ichthyosis (example, Sakai_2009, Khalili_2019, Cho_2017, Kun-Darbois_2016). These data indicate that the variant is very likely to be associated with disease. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as 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: Sep 29, 2024

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