chr9-136673534-T-TCGAGCC

Variant names:

• chr9-136673534-T-TCGAGCC
• rs145169122
• NM_006412.4:c.*212_*217dupGGCTCG

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_006412.4(AGPAT2):​c.*212_*217dupGGCTCG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0905 in 442,506 control chromosomes in the GnomAD database, including 2,305 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.082 (682 hom., cov: 32)
  • Exomes 𝑓: 0.095 (1623 hom.)
• Consequence: AGPAT2 NM_006412.4 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0960
• Publications: 2 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 -16 ACMG points.

• BP6: Variant 9-136673534-T-TCGAGCC is Benign according to our data. Variant chr9-136673534-T-TCGAGCC is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 365909.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.113 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.*212_*217dupGGCTCG		3_prime_UTR	Exon 6 of 6	NP_006403.2
	AGPAT2	NM_001012727.2		c.*212_*217dupGGCTCG		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.*212_*217dupGGCTCG		3_prime_UTR	Exon 6 of 6	ENSP00000360761.2	O15120-1
	AGPAT2	ENST00000371694.7	TSL:1	c.*212_*217dupGGCTCG		3_prime_UTR	Exon 5 of 5	ENSP00000360759.3	O15120-2
	AGPAT2	ENST00000951406.1		c.*212_*217dupGGCTCG		3_prime_UTR	Exon 6 of 6	ENSP00000621465.1

Frequencies

GnomAD3 genomes AF: 0.0822 AC: 12506 AN: 152104 Hom.: 682 Cov.: 32

Gnomad AFR AF: 0.0291

Gnomad AMI AF: 0.0998

Gnomad AMR AF: 0.0900

Gnomad ASJ AF: 0.181

Gnomad EAS AF: 0.00251

Gnomad SAS AF: 0.0341

Gnomad FIN AF: 0.0856

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.121

GnomAD4 exome AF: 0.0949 AC: 27560 AN: 290284 Hom.: 1623 Cov.: 5 AF XY: 0.0958 AC XY: 14218 AN XY: 148410

African (AFR) AF: 0.0313 AC: 241 AN: 7712

American (AMR) AF: 0.0765 AC: 576 AN: 7530

Ashkenazi Jewish (ASJ) AF: 0.169 AC: 1643 AN: 9696

East Asian (EAS) AF: 0.000793 AC: 18 AN: 22690

South Asian (SAS) AF: 0.0273 AC: 286 AN: 10460

European-Finnish (FIN) AF: 0.0830 AC: 1857 AN: 22362

Middle Eastern (MID) AF: 0.148 AC: 206 AN: 1396

European-Non Finnish (NFE) AF: 0.110 AC: 20917 AN: 190552

Other (OTH) AF: 0.102 AC: 1816 AN: 17886

GnomAD4 genome AF: 0.0822 AC: 12507 AN: 152222 Hom.: 682 Cov.: 32 AF XY: 0.0804 AC XY: 5981 AN XY: 74390

African (AFR) AF: 0.0291 AC: 1208 AN: 41564

American (AMR) AF: 0.0899 AC: 1376 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.181 AC: 626 AN: 3468

East Asian (EAS) AF: 0.00251 AC: 13 AN: 5170

South Asian (SAS) AF: 0.0344 AC: 166 AN: 4832

European-Finnish (FIN) AF: 0.0856 AC: 906 AN: 10590

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.115 AC: 7815 AN: 67976

Other (OTH) AF: 0.120 AC: 253 AN: 2116

Alfa AF: 0.0856 Hom.: 61

Bravo AF: 0.0820

Asia WGS AF: 0.0230 AC: 81 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.096
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs145169122; hg19: chr9-139567986; COSMIC: COSV58247153; COSMIC: COSV58247153;