NM_006412.4(AGPAT2):c.809C>T (p.Ala270Val) AND Congenital generalized lipodystrophy type 1

Germline classification:: Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:: Jan 12, 2018
Review status:: criteria provided, conflicting classifications

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:: RCV001169500.5

Allele description [Variation Report for NM_006412.4(AGPAT2):c.809C>T (p.Ala270Val)]

NM_006412.4(AGPAT2):c.809C>T (p.Ala270Val)

Gene:

AGPAT2:1-acylglycerol-3-phosphate O-acyltransferase 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

9q34.3

Genomic location:

Preferred name:

NM_006412.4(AGPAT2):c.809C>T (p.Ala270Val)

HGVS:

NC_000009.12:g.136673780G>A
NG_008090.1:g.18680C>T
NM_001012727.2:c.713C>T
NM_006412.4:c.809C>TMANE SELECT
NP_001012745.1:p.Ala238Val
NP_006403.2:p.Ala270Val
NC_000009.11:g.139568232G>A
NM_006412.3:c.809C>T

Protein change:

A238V

Links:

dbSNP: rs142417583

NCBI 1000 Genomes Browser:

rs142417583

Molecular consequence:

NM_001012727.2:c.713C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_006412.4:c.809C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Congenital generalized lipodystrophy type 1 (CGL1)
Synonyms:: BRUNZELL SYNDROME, AGPAT2-RELATED
Identifiers:: MONDO: MONDO:0012071; MedGen: C1720862; Orphanet: 528; OMIM: 608594

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001332203	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	Benign (Jan 12, 2018)	germline	clinical testing	Citation Link,
SCV004698151	Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic	criteria provided, single submitter (K And H Uppaluri Personalized Medicine Clinic Variant Classification And Assertion Criteria Updated V 2)	Uncertain significance	unknown	research	PubMed (2) [See all records that cite these PMIDs] 11967537, 12826327 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001332203

Illumina Laboratory Services, Illumina

criteria provided, single submitter

(ICSL Variant Classification Criteria 13 December 2019)

Benign
(Jan 12, 2018)

germline

clinical testing

Citation Link,

SCV004698151

Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic

criteria provided, single submitter

(K And H Uppaluri Personalized Medicine Clinic Variant Classification And Assertion Criteria Updated V 2)

Uncertain significance

unknown

research

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

Citations

PubMed

AGPAT2 is mutated in congenital generalized lipodystrophy linked to chromosome 9q34.

Agarwal AK, Arioglu E, De Almeida S, Akkoc N, Taylor SI, Bowcock AM, Barnes RI, Garg A.

Nat Genet. 2002 May;31(1):21-3. Epub 2002 Apr 22.

PubMed [citation]

PMID:: 11967537

Congenital generalized lipodystrophy: significance of triglyceride biosynthetic pathways.

Agarwal AK, Garg A.

Trends Endocrinol Metab. 2003 Jul;14(5):214-21. Review.

PubMed [citation]

PMID:: 12826327

Details of each submission

From Illumina Laboratory Services, Illumina, SCV001332203.1

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

Description

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.

#	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

From Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic, SCV004698151.1

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

Description

Potent mutations in AGPAT2 gene are associated with Congenital generalized lipodystrophy, type 1, which can present with insulin resistance, fatty liver and diabetes. However, the role of this particular variant rs142417583 in Congenital generalized lipodystrophy is yet to be ascertained.

#	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: Mar 16, 2024

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