rs140995132
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_006412.4(AGPAT2):āc.208T>Gā(p.Phe70Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000267 in 1,612,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ).
Frequency
Genomes: š 0.00016 ( 0 hom., cov: 33)
Exomes š: 0.000012 ( 0 hom. )
Consequence
AGPAT2
NM_006412.4 missense
NM_006412.4 missense
Scores
5
13
Clinical Significance
Conservation
PhyloP100: 3.73
Genes affected
AGPAT2 (HGNC:325): (1-acylglycerol-3-phosphate O-acyltransferase 2) This gene encodes a member of the 1-acylglycerol-3-phosphate O-acyltransferase family. The protein is located within the endoplasmic reticulum membrane and converts lysophosphatidic acid to phosphatidic acid, the second step in de novo phospholipid biosynthesis. Mutations in this gene have been associated with congenital generalized lipodystrophy (CGL), or Berardinelli-Seip syndrome, a disease characterized by a near absence of adipose tissue and severe insulin resistance. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.08786598).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AGPAT2 | NM_006412.4 | c.208T>G | p.Phe70Val | missense_variant | 2/6 | ENST00000371696.7 | |
AGPAT2 | NM_001012727.2 | c.208T>G | p.Phe70Val | missense_variant | 2/5 | ||
AGPAT2 | XM_047422636.1 | c.-102T>G | 5_prime_UTR_variant | 2/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AGPAT2 | ENST00000371696.7 | c.208T>G | p.Phe70Val | missense_variant | 2/6 | 1 | NM_006412.4 | P1 | |
AGPAT2 | ENST00000371694.7 | c.208T>G | p.Phe70Val | missense_variant | 2/5 | 1 | |||
AGPAT2 | ENST00000470861.1 | n.216T>G | non_coding_transcript_exon_variant | 2/2 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.000164 AC: 25AN: 152236Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000282 AC: 7AN: 248162Hom.: 0 AF XY: 0.0000296 AC XY: 4AN XY: 135044
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GnomAD4 exome AF: 0.0000123 AC: 18AN: 1460538Hom.: 0 Cov.: 33 AF XY: 0.0000124 AC XY: 9AN XY: 726590
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GnomAD4 genome ? AF: 0.000164 AC: 25AN: 152354Hom.: 0 Cov.: 33 AF XY: 0.000188 AC XY: 14AN XY: 74506
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Monogenic diabetes Uncertain:1
Uncertain significance, criteria provided, single submitter | research | Personalized Diabetes Medicine Program, University of Maryland School of Medicine | Jun 26, 2017 | ACMG Criteria:PP3 (5 predictors), BP4 (4 predictors) - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 26, 2022 | This sequence change replaces phenylalanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 70 of the AGPAT2 protein (p.Phe70Val). This variant is present in population databases (rs140995132, gnomAD 0.06%). This variant has not been reported in the literature in individuals affected with AGPAT2-related conditions. ClinVar contains an entry for this variant (Variation ID: 549536). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Congenital generalized lipodystrophy type 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | May 12, 2022 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
LIST_S2
Benign
T;.;T
M_CAP
Uncertain
D
MetaRNN
Benign
T;T;T
MetaSVM
Uncertain
T
MutationAssessor
Benign
L;L;L
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N
REVEL
Uncertain
Sift
Benign
T;T;T
Sift4G
Benign
T;T;T
Polyphen
B;B;B
Vest4
MVP
MPC
0.21
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at