9-136681035-G-A

Variant names:

• chr9-136681035-G-A
• rs9411216
• NM_006412.4:c.183-3479C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006412.4(AGPAT2):​c.183-3479C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 151,880 control chromosomes in the GnomAD database, including 1,333 homozygotes. 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 0.13 (1333 hom., cov: 32)
• Consequence: AGPAT2 NM_006412.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.545
• Publications: 7 publications found

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.166 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGPAT2	NM_006412.4	c.183-3479C>T		intron_variant	Intron 1 of 5	ENST00000371696.7	NP_006403.2
AGPAT2	NM_001012727.2	c.183-3479C>T		intron_variant	Intron 1 of 4		NP_001012745.1
AGPAT2	XM_047422636.1	c.-127-3479C>T		intron_variant	Intron 1 of 5		XP_047278592.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGPAT2	ENST00000371696.7	c.183-3479C>T		intron_variant	Intron 1 of 5	1	NM_006412.4	ENSP00000360761.2
AGPAT2	ENST00000371694.7	c.183-3479C>T		intron_variant	Intron 1 of 4	1		ENSP00000360759.3
AGPAT2	ENST00000470861.1	n.191-3479C>T		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes AF: 0.127 AC: 19219 AN: 151796 Hom.: 1331 Cov.: 32

Gnomad AFR AF: 0.170

Gnomad AMI AF: 0.124

Gnomad AMR AF: 0.0803

Gnomad ASJ AF: 0.0945

Gnomad EAS AF: 0.00982

Gnomad SAS AF: 0.175

Gnomad FIN AF: 0.100

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.123

Gnomad OTH AF: 0.109

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.127 AC: 19230 AN: 151880 Hom.: 1333 Cov.: 32 AF XY: 0.123 AC XY: 9126 AN XY: 74202

African (AFR) AF: 0.169 AC: 7008 AN: 41350

American (AMR) AF: 0.0800 AC: 1223 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0945 AC: 328 AN: 3470

East Asian (EAS) AF: 0.00985 AC: 51 AN: 5180

South Asian (SAS) AF: 0.176 AC: 844 AN: 4802

European-Finnish (FIN) AF: 0.100 AC: 1054 AN: 10510

Middle Eastern (MID) AF: 0.117 AC: 34 AN: 290

European-Non Finnish (NFE) AF: 0.123 AC: 8340 AN: 67974

Other (OTH) AF: 0.111 AC: 235 AN: 2110

Alfa AF: 0.116 Hom.: 2400

Bravo AF: 0.123

Asia WGS AF: 0.107 AC: 375 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.1
DANN	Benign	0.64
PhyloP100		0.55
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9411216; hg19: chr9-139575487;