NM_012463.4(ATP6V0A2):c.16_19del (p.Arg6fs) AND Cutis laxa with osteodystrophy

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Jan 25, 2023
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:: RCV002789998.3

Allele description [Variation Report for NM_012463.4(ATP6V0A2):c.16_19del (p.Arg6fs)]

NM_012463.4(ATP6V0A2):c.16_19del (p.Arg6fs)

Genes:

LOC130009117:ATAC-STARR-seq lymphoblastoid silent region 5049 [Gene]
ATP6V0A2:ATPase H+ transporting V0 subunit a2 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

12q24.31

Genomic location:

Preferred name:

NM_012463.4(ATP6V0A2):c.16_19del (p.Arg6fs)

Other names:

NM_012463.4:c.16_19del

HGVS:

NC_000012.12:g.123712581_123712584del
NG_012743.1:g.5264_5267del
NM_012463.4:c.16_19delMANE SELECT
NP_036595.2:p.Arg6Alafs
NP_036595.2:p.Arg6fs
NC_000012.11:g.124197128_124197131del
NM_012463.2:c.16_19delCGGA

Protein change:

R6fs

Molecular consequence:

NM_012463.4:c.16_19del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Cutis laxa with osteodystrophy (ARCL2A)
Synonyms:: CUTIS LAXA, AUTOSOMAL RECESSIVE, TYPE IIA; CUTIS LAXA WITH BONE DYSTROPHY; CUTIS LAXA WITH GROWTH AND DEVELOPMENTAL DELAY; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0018163; MedGen: C0268355; OMIM: 219200

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003761318	Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Jan 25, 2023)	germline	curation	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003761318

Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Jan 25, 2023)

germline

curation

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	unknown	not provided	not provided	not provided	not provided	not provided	curation

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 Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard, SCV003761318.1

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

Description

The homozygous p.Gln7LeufsTer7 variant in ATP6V0A2 was identified by our study in two siblings with autosomal recessive cutis laxa type IIA. The p.Gln7LeufsTer7 variant in ATP6V0A2 has not been previously reported in individuals with autosomal recessive cutis laxa type IIA. This variant was absent from large population studies. This variant is predicted to cause a frameshift, which alters the protein‚Äôs amino acid sequence beginning at position 7 and leads to a premature termination codon 7 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Loss of function of the ATP6V0A2 gene is strongly associated to autosomal recessive cutis laxa type IIA. In summary, although additional studies are required to fully establish its clinical significance, this variant is likely pathogenic for autosomal recessive cutis laxa type IIA. ACMG/AMP Criteria applied: PVS1_Strong, PM2_Supporting, PM3 (Richards 2015).

#	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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