NM_173076.3(ABCA12):c.7444C>T (p.Arg2482Ter) AND not provided

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Oct 15, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000480311.6

Allele description

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)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000567262	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Pathogenic (Jul 5, 2018)	germline	clinical testing	Citation Link,
SCV003524973	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 15, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 20672373, 17684380, 28851938, 31168818, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000567262

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Pathogenic
(Jul 5, 2018)

germline

clinical testing

Citation Link,

SCV003524973

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 15, 2023)

germline

clinical testing

PubMed (5)
[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	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

ABCA12 mutations and autosomal recessive congenital ichthyosis: a review of genotype/phenotype correlations and of pathogenetic concepts.

Akiyama M.

Hum Mutat. 2010 Oct;31(10):1090-6. doi: 10.1002/humu.21326. Review.

PubMed [citation]

PMID:: 20672373

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

See all PubMed Citations (5)

Details of each submission

From GeneDx, SCV000567262.4

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

Description

The R2482X pathogenic variant in the ABCA12 gene has been reported previously with another ABCA12 variant in association with harlequin ichthyosis (Akiyama et al., 2007; Koocheck et al., 2014). In one of these patients, immunostaining of a skin biopsy demonstrated complete loss of ABCA12 expression in the epidermis (Akiyama et al., 2007). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The R2482X variant is observed in 1/9,838 (0.01%) alleles from individuals of Ashkenazi Jewish background in large population cohorts (Lek et al., 2016). We interpret R2482X as a pathogenic variant.

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

From Invitae, SCV003524973.2

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

Description

This sequence change creates a premature translational stop signal (p.Arg2482*) in the ABCA12 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ABCA12 are known to be pathogenic (PMID: 20672373). This variant is present in population databases (rs199503269, gnomAD 0.01%). This premature translational stop signal has been observed in individual(s) with congenital ichthyosis (PMID: 17684380, 28851938, 31168818). ClinVar contains an entry for this variant (Variation ID: 419453). For these reasons, this variant has been 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: Jun 23, 2024

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