NM_031443.4(CCM2):c.806G>T (p.Cys269Phe) AND Cerebral cavernous malformation 2

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 17, 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:: RCV002043156.8

Allele description [Variation Report for NM_031443.4(CCM2):c.806G>T (p.Cys269Phe)]

NM_031443.4(CCM2):c.806G>T (p.Cys269Phe)

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.806G>T (p.Cys269Phe)

HGVS:

NC_000007.14:g.45073462G>T
NG_016295.1:g.78275G>T
NM_001029835.2:c.869G>T
NM_001167934.2:c.632G>T
NM_001167935.2:c.533G>T
NM_001363458.2:c.929G>T
NM_001363459.2:c.755G>T
NM_031443.4:c.806G>TMANE SELECT
NP_001025006.1:p.Cys290Phe
NP_001161406.1:p.Cys211Phe
NP_001161407.1:p.Cys178Phe
NP_001350387.1:p.Cys310Phe
NP_001350388.1:p.Cys252Phe
NP_113631.1:p.Cys269Phe
LRG_664t1:c.869G>T
LRG_664:g.78275G>T
LRG_664p1:p.Cys290Phe
NC_000007.13:g.45113061G>T
NR_030770.2:n.888G>T

Protein change:

C178F

Links:

dbSNP: rs2128752334

NCBI 1000 Genomes Browser:

rs2128752334

Molecular consequence:

NM_001029835.2:c.869G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001167934.2:c.632G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001167935.2:c.533G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001363458.2:c.929G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001363459.2:c.755G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_031443.4:c.806G>T - missense variant - [Sequence Ontology: SO:0001583]
NR_030770.2:n.888G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

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

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
SCV002301871	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 17, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002301871

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 17, 2023)

germline

clinical testing

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	clinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group, Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9..

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002301871.4

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

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant¬†is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 1510775). 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). This sequence change replaces cysteine, which is neutral and slightly polar, with phenylalanine, which is neutral and non-polar, at codon 269 of the CCM2 protein (p.Cys269Phe).

#	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: May 25, 2025

ClinVar

Relating variation to medicine