NM_002890.3(RASA1):c.1561_1562dup (p.Asp521fs) AND Capillary malformation-arteriovenous malformation syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 18, 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:: RCV003593577.2

Allele description [Variation Report for NM_002890.3(RASA1):c.1561_1562dup (p.Asp521fs)]

NM_002890.3(RASA1):c.1561_1562dup (p.Asp521fs)

Genes:

RASA1:RAS p21 protein activator 1 [Gene - OMIM - HGNC]
CCNH:cyclin H [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

5q14.3

Genomic location:

Preferred name:

NM_002890.3(RASA1):c.1561_1562dup (p.Asp521fs)

HGVS:

NC_000005.10:g.87363455_87363456dup
NG_011650.1:g.100122_100123dup
NM_001364075.2:c.933+31589_933+31590dup
NM_002890.3:c.1561_1562dupMANE SELECT
NM_022650.3:c.1030_1031dup
NP_002881.1:p.Asp521fs
NP_072179.1:p.Asp344fs
NC_000005.9:g.86659270_86659271insAG
NC_000005.9:g.86659272_86659273dup

Protein change:

D344fs

Molecular consequence:

NM_002890.3:c.1561_1562dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_022650.3:c.1030_1031dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001364075.2:c.933+31589_933+31590dup - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Name:: Capillary malformation-arteriovenous malformation syndrome
Synonyms:: Capillary malformation-arteriovenous malformation
Identifiers:: MONDO: MONDO:0012016; MedGen: C1842180; OMIM: PS608354

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Nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 4 [Mus m...
Nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 4 [Mus musculus]
gi|22137671|gb|AAH28928.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004306937	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jul 18, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 24038909, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004306937

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jul 18, 2023)

germline

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
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

RASA1 mutations and associated phenotypes in 68 families with capillary malformation-arteriovenous malformation.

Revencu N, Boon LM, Mendola A, Cordisco MR, Dubois J, Clapuyt P, Hammer F, Amor DJ, Irvine AD, Baselga E, Dompmartin A, Syed S, Martin-Santiago A, Ades L, Collins F, Smith J, Sandaradura S, Barrio VR, Burrows PE, Blei F, Cozzolino M, Brunetti-Pierri N, et al.

Hum Mutat. 2013 Dec;34(12):1632-41. doi: 10.1002/humu.22431. Epub 2013 Oct 10.

PubMed [citation]

PMID:: 24038909

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, SCV004306937.1

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

Description

For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with RASA1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Asp521Glufs*24) in the RASA1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in RASA1 are known to be pathogenic (PMID: 24038909).

#	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: Oct 13, 2024

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