Genetic Variant AGPAT2:c.*217_*218insGGCTCGAGGGCAGGGGCTCGGGCTCG (chr9-136673534-T-TCGAGCCCGAGCCCCTGCCCTCGAGCC) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_006412.4(AGPAT2):c.*217_*218insGGCTCGAGGGCAGGGGCTCGGGCTCG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000688 in 290,510 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000069 ( 0 hom. )

Consequence

AGPAT2
NM_006412.4 3_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0960

Publications

0 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
lipodystrophy
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
Berardinelli-Seip congenital lipodystrophy
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
neonatal diabetes mellitus
Inheritance: AR Classification: LIMITED Submitted by: Genomics England PanelApp

AGPAT2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGPAT2	NM_006412.4	MANE Select	c.217_218insGGCTCGAGGGCAGGGGCTCGGGCTCG		3_prime_UTR	Exon 6 of 6	NP_006403.2
	AGPAT2	NM_001012727.2		c.217_218insGGCTCGAGGGCAGGGGCTCGGGCTCG		3_prime_UTR	Exon 5 of 5	NP_001012745.1	O15120-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
AGPAT2	ENST00000371696.7	TSL:1 MANE Select	c.217_218insGGCTCGAGGGCAGGGGCTCGGGCTCG	3_prime_UTR	Exon 6 of 6	ENSP00000360761.2	O15120-1
AGPAT2	ENST00000371694.7	TSL:1	c.217_218insGGCTCGAGGGCAGGGGCTCGGGCTCG	3_prime_UTR	Exon 5 of 5	ENSP00000360759.3	O15120-2
AGPAT2	ENST00000951406.1		c.217_218insGGCTCGAGGGCAGGGGCTCGGGCTCG	3_prime_UTR	Exon 6 of 6	ENSP00000621465.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000688

AC:

AN:

290510

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

148526

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

7716

American (AMR)

AF:

0.000133

AC:

AN:

7536

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

9704

East Asian (EAS)

AF:

0.00

AC:

AN:

22690

South Asian (SAS)

AF:

0.00

AC:

AN:

10466

European-Finnish (FIN)

AF:

0.00

AC:

AN:

22378

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1396

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

190724

Other (OTH)

AF:

0.0000559

AC:

AN:

17900

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.725

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.096

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over