9-136677537-G-C

Position:

• chr9-136677537-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_006412.4(AGPAT2):​c.202C>G​(p.Arg68Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,484 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: AGPAT2 NM_006412.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.63

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.913

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AGPAT2	NM_006412.4	c.202C>G	p.Arg68Gly	missense_variant	2/6	ENST00000371696.7	NP_006403.2
AGPAT2	NM_001012727.2	c.202C>G	p.Arg68Gly	missense_variant	2/5		NP_001012745.1
AGPAT2	XM_047422636.1	c.-108C>G		5_prime_UTR_variant	2/6		XP_047278592.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AGPAT2	ENST00000371696.7	c.202C>G	p.Arg68Gly	missense_variant	2/6	1	NM_006412.4	ENSP00000360761.2
AGPAT2	ENST00000371694.7	c.202C>G	p.Arg68Gly	missense_variant	2/5	1		ENSP00000360759.3
AGPAT2	ENST00000470861.1	n.210C>G		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460484 Hom.: 0 Cov.: 33 AF XY: 0.00000275 AC XY: 2 AN XY: 726556

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000236 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.10
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.49	.;T;T
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.47
FATHMM_MKL	Benign	0.30	N
LIST_S2	Benign	0.79	T;.;T
M_CAP	Uncertain	0.20	D
MetaRNN	Pathogenic	0.91	D;D;D
MetaSVM	Uncertain	0.22	D
MutationAssessor	Benign	1.9	L;L;L
PrimateAI	Benign	0.48	T
PROVEAN	Pathogenic	-4.4	D;D;D
REVEL	Pathogenic	0.65
Sift	Benign	0.10	T;T;T
Sift4G	Benign	0.10	T;T;T
Polyphen		0.067	B;B;B
Vest4		0.71
MutPred		0.66		Loss of MoRF binding (P = 0.0038);Loss of MoRF binding (P = 0.0038);Loss of MoRF binding (P = 0.0038);
MVP		0.94
MPC		0.20
ClinPred		0.83	D
GERP RS		4.5
Varity_R		0.25
gMVP		0.83

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

LitVar

Other links and lift over

dbSNP: rs104894093; hg19: chr9-139571989;