NM_031443.4(CCM2):c.30+5_30+6delinsTT AND not provided

Germline classification:: Pathogenic/Likely pathogenic (3 submissions)
Last evaluated:: Aug 2, 2024
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:: RCV000339043.19

Allele description [Variation Report for NM_031443.4(CCM2):c.30+5_30+6delinsTT]

NM_031443.4(CCM2):c.30+5_30+6delinsTT

Genes:

LOC129998395:ATAC-STARR-seq lymphoblastoid silent region 18162 [Gene]
CCM2:CCM2 scaffold protein [Gene - OMIM - HGNC]

Variant type:

Indel

Cytogenetic location:

7p13

Genomic location:

Preferred name:

NM_031443.4(CCM2):c.30+5_30+6delinsTT

HGVS:

NC_000007.14:g.45000368_45000369delinsTT
NG_016295.1:g.5181_5182delinsTT
NM_001167934.2:c.30+5_30+6delinsTT
NM_001167935.2:c.30+5_30+6delinsTT
NM_001363458.2:c.30+5_30+6delinsTT
NM_001363459.2:c.30+5_30+6delinsTT
NM_031443.4:c.30+5_30+6delinsTTMANE SELECT
LRG_664t2:c.30+5_30+6delinsTT
LRG_664:g.5181_5182delinsTT
NC_000007.13:g.45039967_45039968delinsTT
NM_031443.3:c.30+5_30+6delGCinsTT
NM_031443.3:c.30+5_30+6delinsTT

Links:

OMIM: 607929.0010; dbSNP: rs797044623

NCBI 1000 Genomes Browser:

rs797044623

Molecular consequence:

NM_001167934.2:c.30+5_30+6delinsTT - intron variant - [Sequence Ontology: SO:0001627]
NM_001167935.2:c.30+5_30+6delinsTT - intron variant - [Sequence Ontology: SO:0001627]
NM_001363458.2:c.30+5_30+6delinsTT - intron variant - [Sequence Ontology: SO:0001627]
NM_001363459.2:c.30+5_30+6delinsTT - intron variant - [Sequence Ontology: SO:0001627]
NM_031443.4:c.30+5_30+6delinsTT - intron variant - [Sequence Ontology: SO:0001627]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

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MAG: Clostridiaceae bacterium DTU059, whole genome shotgun sequencing project
MAG: Clostridiaceae bacterium DTU059, whole genome shotgun sequencing project
gi|973680745|gb|LFSK00000000.1|LFSK 000

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000224657	Eurofins Ntd Llc (ga)	criteria provided, single submitter (EGL Classification Definitions 2015)	Pathogenic (Mar 11, 2015)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 21543988, 23595507 Citation Link,
SCV000329216	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Aug 2, 2024)	germline	clinical testing	Citation Link,
SCV000612714	Athena Diagnostics	criteria provided, single submitter (Athena Diagnostics Criteria)	Likely pathogenic (Jun 6, 2023)	unknown	clinical testing	PubMed (4) [See all records that cite these PMIDs] 33729445, 21543988, 23595507, 26467025

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000224657

Eurofins Ntd Llc (ga)

criteria provided, single submitter

(EGL Classification Definitions 2015)

Pathogenic
(Mar 11, 2015)

germline

clinical testing

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

Citation Link,

SCV000329216

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Aug 2, 2024)

germline

clinical testing

Citation Link,

SCV000612714

Athena Diagnostics

criteria provided, single submitter

(Athena Diagnostics Criteria)

Likely pathogenic
(Jun 6, 2023)

unknown

clinical testing

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

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	1	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Cerebral Cavernous Malformation 2 Syndrome Presenting With Retinal Cavernous Hemangioma and Sixth Cranial Nerve Palsy.

Khan MJ, Dinkin M, D'Amico DJ.

JAMA Ophthalmol. 2021 Mar 1;139(3):e204104. doi: 10.1001/jamaophthalmol.2020.4104. Epub 2021 Mar 17. No abstract available.

PubMed [citation]

PMID:: 33729445

A founder mutation in the Ashkenazi Jewish population affecting messenger RNA splicing of the CCM2 gene causes cerebral cavernous malformations.

Gallione CJ, Solatycki A, Awad IA, Weber JL, Marchuk DA.

Genet Med. 2011 Jul;13(7):662-6. doi: 10.1097/GIM.0b013e318211ff8b.

PubMed [citation]

PMID:: 21543988
PMCID:: PMC3132303

See all PubMed Citations (4)

Details of each submission

From Eurofins Ntd Llc (ga), SCV000224657.5

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

#	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		1	not provided	not provided	not provided

From GeneDx, SCV000329216.12

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

Description

Non-canonical splice site variant demonstrated to result in loss-of-function (PMID: 21543988, 23595507); This variant is associated with the following publications: (PMID: 23595507, 33729445, 21543988)

#	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

From Athena Diagnostics, SCV000612714.3

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

Description

The frequency of this variant in the general population is consistent with pathogenicity (http://gnomad.broadinstitute.org). This variant has been identified in multiple unrelated individuals with clinical features associated with this gene. Assessment of experimental evidence suggests this variant results in abnormal RNA splicing (PMID: 21543988, 23595507).

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

Last Updated: Oct 8, 2024

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