NM_000071.3(CBS):c.536_553del (p.Asp179_Leu184del) AND Familial thoracic aortic aneurysm and aortic dissection

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Nov 3, 2022
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:: RCV004020154.1

Allele description [Variation Report for NM_000071.3(CBS):c.536_553del (p.Asp179_Leu184del)]

NM_000071.3(CBS):c.536_553del (p.Asp179_Leu184del)

Gene:

CBS:cystathionine beta-synthase [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

21q22.3

Genomic location:

Preferred name:

NM_000071.3(CBS):c.536_553del (p.Asp179_Leu184del)

HGVS:

NC_000021.9:g.43065503_43065520del
NG_008938.1:g.15414_15431del
NM_000071.3:c.536_553delMANE SELECT
NM_001178008.3:c.536_553del
NM_001178009.3:c.536_553del
NM_001320298.2:c.536_553del
NM_001321072.1:c.221_238del
NP_000062.1:p.Asp179_Leu184del
NP_000062.1:p.Asp179_Leu184del
NP_001171479.1:p.Asp179_Leu184del
NP_001171480.1:p.Asp179_Leu184del
NP_001307227.1:p.Asp179_Leu184del
NP_001308001.1:p.Asp74_Leu79del
LRG_777t1:c.536_553del
LRG_777:g.15414_15431del
LRG_777p1:p.Asp179_Leu184del
NC_000021.8:g.44485610_44485627del
NC_000021.8:g.44485613_44485630del
NM_000071.2:c.536_553del
NM_000071.2:c.536_553del18
NM_000071.2:c.536_553delACGTGCTGCGGGCACTGG
p.(D179_L184del)

Links:

dbSNP: rs794727835

NCBI 1000 Genomes Browser:

rs794727835

Molecular consequence:

NM_000071.3:c.536_553del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001178008.3:c.536_553del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001178009.3:c.536_553del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001320298.2:c.536_553del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001321072.1:c.221_238del - inframe_deletion - [Sequence Ontology: SO:0001822]

Condition(s)

Name:: Familial thoracic aortic aneurysm and aortic dissection (TAAD)
Synonyms:: Thoracic aortic aneurysm and aortic dissection; Thoracic aortic aneurysms and dissections
Identifiers:: MONDO: MONDO:0019625; MedGen: C4707243; Orphanet: 91387; OMIM: PS607086

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003645655	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Likely pathogenic (Nov 3, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 12124992, 24138954 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003645655

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Likely pathogenic
(Nov 3, 2022)

germline

clinical testing

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

Citation Link

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

The molecular basis of cystathionine beta-synthase deficiency in Australian patients: genotype-phenotype correlations and response to treatment.

Gaustadnes M, Wilcken B, Oliveriusova J, McGill J, Fletcher J, Kraus JP, Wilcken DE.

Hum Mutat. 2002 Aug;20(2):117-26.

PubMed [citation]

PMID:: 12124992

Cystathionine beta-synthase deficiency heralded by cerebral sinus venous thrombosis and stroke.

Ruhoy IS, Merritt JL 2nd, Amlie-Lefond C.

Pediatr Neurol. 2014 Jan;50(1):108-11. doi: 10.1016/j.pediatrneurol.2013.08.021. Epub 2013 Oct 15.

PubMed [citation]

PMID:: 24138954

Details of each submission

From Ambry Genetics, SCV003645655.2

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

Description

The c.536_553del18 (p.D179_L184del) alteration is located in exon 7 (coding exon 5) of the CBS gene. This alteration consists of an in-frame deletion of 18 nucleotides between nucleotide positions c.536 and c.553, resulting in the deletion of <NA> residues. This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This variant has been reported in several individuals with CBS-related homocystinuria and a second variant (Ruhoy, 2014; Gaustadnes, 2002) including one individual with a dislocated lens, mild developmental delay and intellectual disability and a Marfanoid habitus (Gaustadnes, 2002). This alteration is predicted to be deleterious by in silico analysis (Choi, 2012). Based on the available evidence, this alteration is classified as likely pathogenic.

#	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: Nov 3, 2024

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