rs1057517656

Positions:

• chr9-136673825-GTGGTCCTCA-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PM4

The NM_006412.4(AGPAT2):​c.755_763delTGAGGACCA​(p.Met252_Thr254del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.000000687 in 1,454,740 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as not provided (no stars).

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: AGPAT2 NM_006412.4 disruptive_inframe_deletion
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 6.78

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
• PM4: Nonframeshift variant in NON repetitive region in NM_006412.4.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AGPAT2	NM_006412.4	c.755_763delTGAGGACCA	p.Met252_Thr254del	disruptive_inframe_deletion	6/6	ENST00000371696.7	NP_006403.2
AGPAT2	NM_001012727.2	c.659_667delTGAGGACCA	p.Met220_Thr222del	disruptive_inframe_deletion	5/5		NP_001012745.1
AGPAT2	XM_047422636.1	c.446_454delTGAGGACCA	p.Met149_Thr151del	disruptive_inframe_deletion	6/6		XP_047278592.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AGPAT2	ENST00000371696.7	c.755_763delTGAGGACCA	p.Met252_Thr254del	disruptive_inframe_deletion	6/6	1	NM_006412.4	ENSP00000360761.2
AGPAT2	ENST00000371694.7	c.659_667delTGAGGACCA	p.Met220_Thr222del	disruptive_inframe_deletion	5/5	1		ENSP00000360759.3
AGPAT2	ENST00000472820.1	n.683_691delTGAGGACCA		non_coding_transcript_exon_variant	4/4	1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1454740 Hom.: 0 AF XY: 0.00000138 AC XY: 1 AN XY: 723282

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: 0.0000118

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

Submissions by phenotype

Congenital generalized lipodystrophy type 1 Other:1

not provided, no classification provided

literature only

GeneReviews

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1057517656; hg19: chr9-139568277;