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NM_031443.4(CCM2):c.499C>T (p.Gln167Ter) AND Cerebral cavernous malformation 2

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Apr 10, 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:
RCV003605337.1

Allele description [Variation Report for NM_031443.4(CCM2):c.499C>T (p.Gln167Ter)]

NM_031443.4(CCM2):c.499C>T (p.Gln167Ter)

Gene:
CCM2:CCM2 scaffold protein [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
7p13
Genomic location:
Preferred name:
NM_031443.4(CCM2):c.499C>T (p.Gln167Ter)
HGVS:
  • NC_000007.14:g.45068469C>T
  • NG_016295.1:g.73282C>T
  • NM_001029835.2:c.562C>T
  • NM_001167934.2:c.325C>T
  • NM_001167935.2:c.472+3823C>T
  • NM_001363458.2:c.499C>T
  • NM_001363459.2:c.325C>T
  • NM_031443.4:c.499C>TMANE SELECT
  • NP_001025006.1:p.Gln188Ter
  • NP_001161406.1:p.Gln109Ter
  • NP_001350387.1:p.Gln167Ter
  • NP_001350388.1:p.Gln109Ter
  • NP_113631.1:p.Gln167Ter
  • NP_113631.1:p.Gln167Ter
  • LRG_664t1:c.562C>T
  • LRG_664t2:c.499C>T
  • LRG_664:g.73282C>T
  • LRG_664p1:p.Gln188Ter
  • LRG_664p2:p.Gln167Ter
  • NC_000007.13:g.45108068C>T
  • NM_031443.3:c.499C>T
  • NR_030770.2:n.581C>T
Protein change:
Q109*
Molecular consequence:
  • NM_001167935.2:c.472+3823C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NR_030770.2:n.581C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NM_001029835.2:c.562C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001167934.2:c.325C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001363458.2:c.499C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001363459.2:c.325C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_031443.4:c.499C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:
Cerebral cavernous malformation 2
Synonyms:
Cerebral cavernous malformations 2
Identifiers:
MONDO: MONDO:0011304; MedGen: C1864041; Orphanet: 221061; OMIM: 603284

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004457443Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Apr 10, 2023) 		germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Novel CCM1, CCM2, and CCM3 mutations in patients with cerebral cavernous malformations: in-frame deletion in CCM2 prevents formation of a CCM1/CCM2/CCM3 protein complex.

Stahl S, Gaetzner S, Voss K, Brackertz B, Schleider E, Sürücü O, Kunze E, Netzer C, Korenke C, Finckh U, Habek M, Poljakovic Z, Elbracht M, Rudnik-Schöneborn S, Bertalanffy H, Sure U, Felbor U.

Hum Mutat. 2008 May;29(5):709-17. doi: 10.1002/humu.20712.

PubMed [citation]
PMID:
18300272

High mutation detection rates in cerebral cavernous malformation upon stringent inclusion criteria: one-third of probands are minors.

Spiegler S, Najm J, Liu J, Gkalympoudis S, Schröder W, Borck G, Brockmann K, Elbracht M, Fauth C, Ferbert A, Freudenberg L, Grasshoff U, Hellenbroich Y, Henn W, Hoffjan S, Hüning I, Korenke GC, Kroisel PM, Kunstmann E, Mair M, Munk-Schulenburg S, Nikoubashman O, et al.

Mol Genet Genomic Med. 2014 Mar;2(2):176-85. doi: 10.1002/mgg3.60. Epub 2014 Jan 14.

PubMed [citation]
PMID:
24689081
PMCID:
PMC3960060
See all PubMed Citations (3)

Details of each submission

From Invitae, SCV004457443.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

This sequence change creates a premature translational stop signal (p.Gln167*) in the CCM2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CCM2 are known to be pathogenic (PMID: 18300272, 24689081). For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with CCM2-related conditions. This variant is not present in population databases (gnomAD no frequency).

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Feb 28, 2024