rs140995132

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_006412.4(AGPAT2):​c.208T>G​(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 (★★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

AGPAT2
NM_006412.4 missense

Scores

5
13

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:3

Conservation

PhyloP100: 3.73

Publications

1 publications found
Variant links:
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]
AGPAT2 Gene-Disease associations (from GenCC):
  • congenital generalized lipodystrophy type 1
    Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
  • Berardinelli-Seip congenital lipodystrophy
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
  • neonatal diabetes mellitus
    Inheritance: AR Classification: LIMITED Submitted by: Genomics England PanelApp

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.08786598).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006412.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
AGPAT2
NM_006412.4
MANE Select
c.208T>Gp.Phe70Val
missense
Exon 2 of 6NP_006403.2
AGPAT2
NM_001012727.2
c.208T>Gp.Phe70Val
missense
Exon 2 of 5NP_001012745.1

Ensembl Transcripts

Selected
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
AGPAT2
ENST00000371696.7
TSL:1 MANE Select
c.208T>Gp.Phe70Val
missense
Exon 2 of 6ENSP00000360761.2
AGPAT2
ENST00000371694.7
TSL:1
c.208T>Gp.Phe70Val
missense
Exon 2 of 5ENSP00000360759.3
AGPAT2
ENST00000470861.1
TSL:2
n.216T>G
non_coding_transcript_exon
Exon 2 of 2

Frequencies

GnomAD3 genomes
AF:
0.000164
AC:
25
AN:
152236
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000603
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.0000282
AC:
7
AN:
248162
AF XY:
0.0000296
show subpopulations
Gnomad AFR exome
AF:
0.000438
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000123
AC:
18
AN:
1460538
Hom.:
0
Cov.:
33
AF XY:
0.0000124
AC XY:
9
AN XY:
726590
show subpopulations
African (AFR)
AF:
0.000508
AC:
17
AN:
33476
American (AMR)
AF:
0.00
AC:
0
AN:
44718
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26122
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39694
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86254
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
52228
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1111910
Other (OTH)
AF:
0.0000166
AC:
1
AN:
60368
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.489
Heterozygous variant carriers
0
2
3
5
6
8
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.000164
AC:
25
AN:
152354
Hom.:
0
Cov.:
33
AF XY:
0.000188
AC XY:
14
AN XY:
74506
show subpopulations
African (AFR)
AF:
0.000601
AC:
25
AN:
41582
American (AMR)
AF:
0.00
AC:
0
AN:
15312
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3472
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5188
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4830
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10630
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
68020
Other (OTH)
AF:
0.00
AC:
0
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.513
Heterozygous variant carriers
0
2
4
5
7
9
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.000270
Hom.:
0
Bravo
AF:
0.000268
ESP6500AA
AF:
0.000454
AC:
2
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000742
AC:
9
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance
Revision:criteria provided, multiple submitters, no conflicts
View on ClinVar
Pathogenic
VUS
Benign
Condition
-
1
-
Congenital generalized lipodystrophy type 1 (1)
-
1
-
Monogenic diabetes (1)
-
1
-
not provided (1)

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.49
BayesDel_addAF
Benign
-0.19
T
BayesDel_noAF
Benign
-0.13
CADD
Benign
21
DANN
Benign
0.80
DEOGEN2
Benign
0.11
T
Eigen
Benign
-0.29
Eigen_PC
Benign
-0.13
FATHMM_MKL
Benign
0.66
D
LIST_S2
Benign
0.75
T
M_CAP
Uncertain
0.17
D
MetaRNN
Benign
0.088
T
MetaSVM
Uncertain
-0.077
T
MutationAssessor
Benign
1.7
L
PhyloP100
3.7
PrimateAI
Uncertain
0.66
T
PROVEAN
Benign
-1.2
N
REVEL
Uncertain
0.34
Sift
Benign
0.83
T
Sift4G
Benign
0.34
T
Polyphen
0.0040
B
Vest4
0.45
MVP
0.97
MPC
0.21
ClinPred
0.061
T
GERP RS
4.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.8
Varity_R
0.14
gMVP
0.62
Mutation Taster
=71/29
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs140995132; hg19: chr9-139571983; API