NM_006412.4(AGPAT2):c.475C>T (p.Arg159Cys) AND Congenital generalized lipodystrophy type 1

Germline classification:: Benign (2 submissions)
Last evaluated:: Apr 27, 2017
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:: RCV001167076.8

Allele description [Variation Report for NM_006412.4(AGPAT2):c.475C>T (p.Arg159Cys)]

NM_006412.4(AGPAT2):c.475C>T (p.Arg159Cys)

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.475C>T (p.Arg159Cys)

Other names:

p.Arg159Cys

HGVS:

NC_000009.12:g.136676978G>A
NG_008090.1:g.15482C>T
NM_001012727.2:c.475C>T
NM_006412.4:c.475C>TMANE SELECT
NP_001012745.1:p.Arg159Cys
NP_006403.2:p.Arg159Cys
NC_000009.11:g.139571430G>A
NM_006412.3:c.475C>T

Protein change:

R159C

Links:

dbSNP: rs142993240

NCBI 1000 Genomes Browser:

rs142993240

Molecular consequence:

NM_001012727.2:c.475C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_006412.4:c.475C>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
SCV001329520	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	Benign (Apr 27, 2017)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001329520

Illumina Laboratory Services, Illumina

criteria provided, single submitter

(ICSL Variant Classification Criteria 13 December 2019)

Benign
(Apr 27, 2017)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

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
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	research

Citations

PubMed

Truncation of POC1A associated with short stature and extreme insulin resistance.

Chen JH, Segni M, Payne F, Huang-Doran I, Sleigh A, Adams C; UK10K Consortium, Savage DB, O'Rahilly S, Semple RK, Barroso I.

J Mol Endocrinol. 2015 Oct;55(2):147-58. doi: 10.1530/JME-15-0090.

PubMed [citation]

PMID:: 26336158
PMCID:: PMC4722288

Congenital Generalized Lipoatrophy (Berardinelli-Seip Syndrome) Type 1: Description of Novel AGPAT2 Homozygous Variants Showing the Highly Heterogeneous Presentation of the Disease.

Ceccarini G, Magno S, Pelosini C, Ferrari F, Sessa MR, Scabia G, Maffei M, Jéru I, Lascols O, Vigouroux C, Santini F.

Front Endocrinol (Lausanne). 2020;11:39. doi: 10.3389/fendo.2020.00039.

PubMed [citation]

PMID:: 32117065
PMCID:: PMC7034310

Details of each submission

From Illumina Laboratory Services, Illumina, SCV001329520.1

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

Description

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign.

#	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, SCV004698173.1

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

Description

Potent mutations in AGPAT2 gene are associated with Congenital generalized lipodystrophy, type 1, which can present with insulin resistance, fatty liver and diabetes. rs142993240 variant is prevalent with Congenital Generalized Lipoatrophy. However, the role of this rs142993240 particular variant 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

Flagged submissions

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004698173	Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic	flagged submission Reason: Outlier claim with insufficient supporting evidence Notes: Also, submission does not include any variant-specific evidence, but just mentions the gene-disease relationship. (K And H Uppaluri Personalized Medicine Clinic Variant Classification And Assertion Criteria Updated V 2)	Uncertain risk allele	unknown	research	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004698173

Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic

flagged submission

Reason: Outlier claim with insufficient supporting evidence

Notes: Also, submission does not include any variant-specific evidence, but just mentions the gene-disease relationship.

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

Uncertain risk allele

unknown

research

PubMed (1)
[See all records that cite this PMID]

Citation Link

Last Updated: Jun 22, 2025

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