GeneBe

9-136681035-G-C

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_006412.4(AGPAT2):​c.183-3479C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000659 in 151,830 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

AGPAT2
NM_006412.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.545

Publications

7 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.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.91).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
AGPAT2NM_006412.4 linkc.183-3479C>G intron_variant Intron 1 of 5 ENST00000371696.7 NP_006403.2 O15120-1A0A024R8I7
AGPAT2NM_001012727.2 linkc.183-3479C>G intron_variant Intron 1 of 4 NP_001012745.1 O15120-2A0A024R8F9
AGPAT2XM_047422636.1 linkc.-127-3479C>G intron_variant Intron 1 of 5 XP_047278592.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
AGPAT2ENST00000371696.7 linkc.183-3479C>G intron_variant Intron 1 of 5 1 NM_006412.4 ENSP00000360761.2 O15120-1
AGPAT2ENST00000371694.7 linkc.183-3479C>G intron_variant Intron 1 of 4 1 ENSP00000360759.3 O15120-2
AGPAT2ENST00000470861.1 linkn.191-3479C>G intron_variant Intron 1 of 1 2

Frequencies

GnomAD3 genomes
AF:
0.00000659
AC:
1
AN:
151830
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
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
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.00000659
AC:
1
AN:
151830
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74120
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
41268
American (AMR)
AF:
0.0000655
AC:
1
AN:
15266
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3470
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5192
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4818
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10512
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
314
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
67988
Other (OTH)
AF:
0.00
AC:
0
AN:
2090
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.425
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
0.00
Hom.:
2400
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.91
CADD
Benign
1.3
DANN
Benign
0.46
PhyloP100
0.55

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: rs9411216; hg19: chr9-139575487; API