NM_006412.4:c.*354C>G

Variant names:

• chr9-136673398-G-C
• rs886063719
• NM_006412.4:c.*354C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006412.4(AGPAT2):​c.*354C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000217 in 46,024 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: not found (cov: 34)
  • Exomes 𝑓: 0.000022 (0 hom.)
• Consequence: AGPAT2 NM_006412.4 3_prime_UTR
• Scores: Splicing: ADA: 0.00003789
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.756
• Publications: 0 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
• 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

ACMG classification

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).

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.*354C>G		3_prime_UTR	Exon 6 of 6	NP_006403.2
	AGPAT2	NM_001012727.2		c.*354C>G		3_prime_UTR	Exon 5 of 5	NP_001012745.1	O15120-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGPAT2	ENST00000371696.7	TSL:1 MANE Select	c.*354C>G		3_prime_UTR	Exon 6 of 6	ENSP00000360761.2	O15120-1
	AGPAT2	ENST00000371694.7	TSL:1	c.*354C>G		3_prime_UTR	Exon 5 of 5	ENSP00000360759.3	O15120-2
	AGPAT2	ENST00000951406.1		c.*354C>G		3_prime_UTR	Exon 6 of 6	ENSP00000621465.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.0000217 AC: 1 AN: 46024 Hom.: 0 Cov.: 0 AF XY: 0.0000432 AC XY: 1 AN XY: 23146

African (AFR) AF: 0.00 AC: 0 AN: 1772

American (AMR) AF: 0.00 AC: 0 AN: 1178

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1962

East Asian (EAS) AF: 0.00 AC: 0 AN: 3224

South Asian (SAS) AF: 0.00 AC: 0 AN: 1528

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2650

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 278

European-Non Finnish (NFE) AF: 0.0000330 AC: 1 AN: 30264

Other (OTH) AF: 0.00 AC: 0 AN: 3168

GnomAD4 genome Cov.: 34

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.40
DANN	Benign	0.38
PhyloP100		-0.76

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000038
dbscSNV1_RF	Benign	0.0
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: rs886063719; hg19: chr9-139567850;