NM_000821.7(GGCX):c.1609G>T (p.Gly537Ter) AND Body skin hyperlaxity due to vitamin K-dependent coagulation factor deficiency

Germline classification:: Pathogenic (1 submission)
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:: RCV001290234.1

Allele description [Variation Report for NM_000821.7(GGCX):c.1609G>T (p.Gly537Ter)]

NM_000821.7(GGCX):c.1609G>T (p.Gly537Ter)

Gene:

GGCX:gamma-glutamyl carboxylase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2p11.2

Genomic location:

Preferred name:

NM_000821.7(GGCX):c.1609G>T (p.Gly537Ter)

HGVS:

NC_000002.12:g.85551812C>A
NG_011811.2:g.14723G>T
NM_000821.7:c.1609G>TMANE SELECT
NM_001142269.4:c.1438G>T
NP_000812.2:p.Gly537Ter
NP_001135741.1:p.Gly480Ter
LRG_592t1:c.1609G>T
LRG_592:g.14723G>T
LRG_592p1:p.Gly537Ter
NC_000002.11:g.85778935C>A
NM_000821.6:c.1609G>T

Protein change:

G480*

Links:

dbSNP: rs1691965570

NCBI 1000 Genomes Browser:

rs1691965570

Molecular consequence:

NM_000821.7:c.1609G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001142269.4:c.1438G>T - nonsense - [Sequence Ontology: SO:0001587]

Functional consequence:

cryptic splice donor activation [Variation Ontology: 0374]

Observations:

Condition(s)

Name:: Body skin hyperlaxity due to vitamin K-dependent coagulation factor deficiency
Synonyms:: PXE-LIKE DISORDER WITH MULTIPLE COAGULATION FACTOR DEFICIENCY; Pseudoxanthoma elasticum-like disorder with multiple coagulation factor deficiency
Identifiers:: MONDO: MONDO:0012570; MedGen: C1835813; Orphanet: 91135; OMIM: 610842

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001478101	Division of Biology and Genetics, University of Brescia	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic	paternal	clinical testing	PubMed (2) [See all records that cite these PMIDs] 25741868, 29175035

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001478101

Division of Biology and Genetics, University of Brescia

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic

paternal

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
caucasian	paternal	yes	1	not provided	not provided	not provided	not provided	clinical testing

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

Characterization of a Pseudoxanthoma elasticum-like patient with coagulation deficiency, cutaneous calcinosis and GGCX compound heterozygosity.

Dordoni C, Gatti M, Venturini M, Zanca A, Cinquina V, Santoro G, Battocchio S, Calzavara-Pinton P, Ritelli M, Colombi M.

J Dermatol Sci. 2018 Feb;89(2):201-204. doi: 10.1016/j.jdermsci.2017.11.009. Epub 2017 Nov 22. Review. No abstract available.

PubMed [citation]

PMID:: 29175035

Details of each submission

From Division of Biology and Genetics, University of Brescia, SCV001478101.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	caucasian	1	not provided	not provided	clinical testing	PubMed (2)

Description

The paternal variant (last nucleotide of the exon) was predicted to alter the canonical splice donor site by splicing evaluation tools of the Alamut software. Characterization of the splicing effect showed the presence of a minor aberrant band with lower molecular weight. Sequencing of the wild-type fragment showed homozygosity disclosed the deletion of the last 25 nucleotides of exon 11 (r.1585_1609del), demonstrating that the paternal c.1609G>T variant, though formally a nonsense mutation, leads to the activation of a cryptic splice donor site within exon 11 between cDNA nucleotides 1584 and 1585, (p.Val529Aspfs*8) undergoing to a certain degree nonsense mediated RNA decay.

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

Last Updated: Apr 23, 2022

ClinVar

Relating variation to medicine