9-136673673-G-C

Variant names:

• chr9-136673673-G-C
• rs112657922
• NM_006412.4:c.*79C>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006412.4(AGPAT2):​c.*79C>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 0.00439 in 1,408,574 control chromosomes in the GnomAD database, including 144 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.018 (76 hom., cov: 34)
  • Exomes 𝑓: 0.0027 (68 hom.)
• Consequence: AGPAT2 NM_006412.4 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -1.68
• 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 9-136673673-G-C is Benign according to our data. Variant chr9-136673673-G-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 365914.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0586 is higher than 0.05.

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.*79C>G		3_prime_UTR	Exon 6 of 6	NP_006403.2
	AGPAT2	NM_001012727.2		c.*79C>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.*79C>G		3_prime_UTR	Exon 6 of 6	ENSP00000360761.2	O15120-1
	AGPAT2	ENST00000371694.7	TSL:1	c.*79C>G		3_prime_UTR	Exon 5 of 5	ENSP00000360759.3	O15120-2
	AGPAT2	ENST00000951406.1		c.*79C>G		3_prime_UTR	Exon 6 of 6	ENSP00000621465.1

Frequencies

GnomAD3 genomes AF: 0.0183 AC: 2788 AN: 152148 Hom.: 73 Cov.: 34

Gnomad AFR AF: 0.0601

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0107

Gnomad ASJ AF: 0.0101

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000971

Gnomad OTH AF: 0.0134

GnomAD4 exome AF: 0.00269 AC: 3377 AN: 1256308 Hom.: 68 Cov.: 21 AF XY: 0.00241 AC XY: 1472 AN XY: 611780

African (AFR) AF: 0.0687 AC: 1873 AN: 27250

American (AMR) AF: 0.00516 AC: 127 AN: 24622

Ashkenazi Jewish (ASJ) AF: 0.00830 AC: 166 AN: 20004

East Asian (EAS) AF: 0.00 AC: 0 AN: 32216

South Asian (SAS) AF: 0.000247 AC: 16 AN: 64814

European-Finnish (FIN) AF: 0.000136 AC: 6 AN: 44100

Middle Eastern (MID) AF: 0.0140 AC: 50 AN: 3582

European-Non Finnish (NFE) AF: 0.000777 AC: 767 AN: 987594

Other (OTH) AF: 0.00714 AC: 372 AN: 52126

GnomAD4 genome AF: 0.0185 AC: 2812 AN: 152266 Hom.: 76 Cov.: 34 AF XY: 0.0179 AC XY: 1330 AN XY: 74454

African (AFR) AF: 0.0605 AC: 2516 AN: 41554

American (AMR) AF: 0.0107 AC: 164 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0101 AC: 35 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10616

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000971 AC: 66 AN: 67994

Other (OTH) AF: 0.0133 AC: 28 AN: 2110

Alfa AF: 0.000704 Hom.: 0

Bravo AF: 0.0209

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Congenital generalized lipodystrophy type 1 (2)
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.13
DANN	Benign	0.56
PhyloP100		-1.7
Mutation Taster		=100/0	polymorphism

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: rs112657922; hg19: chr9-139568125;