NM_001171.6(ABCC6):c.4104del (p.Asp1368fs) AND not provided

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Nov 27, 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:: RCV001857050.6

Allele description [Variation Report for NM_001171.6(ABCC6):c.4104del (p.Asp1368fs)]

NM_001171.6(ABCC6):c.4104del (p.Asp1368fs)

Gene:

ABCC6:ATP binding cassette subfamily C member 6 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

16p13.11

Genomic location:

Preferred name:

NM_001171.6(ABCC6):c.4104del (p.Asp1368fs)

HGVS:

NC_000016.10:g.16154732del
NG_007558.3:g.73886del
NM_001171.6:c.4104delMANE SELECT
NM_001351800.1:c.3762del
NP_001162.5:p.Asp1368fs
NP_001338729.1:p.Asp1254fs
LRG_1115t1:c.4104del
LRG_1115:g.73886del
LRG_1115p1:p.Asp1368fs
NC_000016.9:g.16248589del
NG_007558.2:g.73740del
NM_001171.5:c.4104del
NM_001171.5:c.4104delC
NR_147784.1:n.3766del

Protein change:

D1254fs

Links:

dbSNP: rs72664237

NCBI 1000 Genomes Browser:

rs72664237

Molecular consequence:

NM_001171.6:c.4104del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001351800.1:c.3762del - frameshift variant - [Sequence Ontology: SO:0001589]
NR_147784.1:n.3766del - non-coding transcript variant - [Sequence Ontology: SO:0001619]

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
SCV002243399	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 27, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 17617515, 11536079, 31164056, 28492532
SCV002547087	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Jan 7, 2022)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002243399

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 27, 2023)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

SCV002547087

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Jan 7, 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	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

Mutation detection in the ABCC6 gene and genotype-phenotype analysis in a large international case series affected by pseudoxanthoma elasticum.

Pfendner EG, Vanakker OM, Terry SF, Vourthis S, McAndrew PE, McClain MR, Fratta S, Marais AS, Hariri S, Coucke PJ, Ramsay M, Viljoen D, Terry PF, De Paepe A, Uitto J, Bercovitch LG.

J Med Genet. 2007 Oct;44(10):621-8. Epub 2007 Jul 6.

PubMed [citation]

PMID:: 17617515
PMCID:: PMC2597973

A spectrum of ABCC6 mutations is responsible for pseudoxanthoma elasticum.

Le Saux O, Beck K, Sachsinger C, Silvestri C, Treiber C, Göring HH, Johnson EW, De Paepe A, Pope FM, Pasquali-Ronchetti I, Bercovitch L, Marais AS, Viljoen DL, Terry SF, Boyd CD.

Am J Hum Genet. 2001 Oct;69(4):749-64. Epub 2001 Aug 31. Erratum in: Am J Hum Genet 2001 Dec;69(6):1413. Am J Hum Genet 2002 Aug;71(2):448.

PubMed [citation]

PMID:: 11536079
PMCID:: PMC1226061

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002243399.3

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

Description

This sequence change creates a premature translational stop signal (p.Asp1368Glufs*35) in the ABCC6 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ABCC6 are known to be pathogenic (PMID: 11536079, 17617515). This variant is present in population databases (rs72664237, gnomAD 0.004%). This premature translational stop signal has been observed in individual(s) with clinical features of pseudoxanthoma elasticum (PMID: 11536079, 31164056). ClinVar contains an entry for this variant (Variation ID: 433350). 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

From GeneDx, SCV002547087.2

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

Description

Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 29722917, 32581362, 11536079, 31164056)

#	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

Last Updated: Sep 29, 2024

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