9-136673534-T-TCGAGCC

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_006412.4(AGPAT2):c.*217_*218insGGCTCG 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

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]

ACMG classification

Verdict is Benign. Variant got -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 [Likely_benign]. Clinvar id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AGPAT2	NM_006412.4	c.*217_*218insGGCTCG		3_prime_UTR_variant	6/6	ENST00000371696.7
AGPAT2	NM_001012727.2	c.*217_*218insGGCTCG		3_prime_UTR_variant	5/5
AGPAT2	XM_047422636.1	c.*217_*218insGGCTCG		3_prime_UTR_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AGPAT2	ENST00000371696.7	c.*217_*218insGGCTCG		3_prime_UTR_variant	6/6	1	NM_006412.4	P1
AGPAT2	ENST00000371694.7	c.*217_*218insGGCTCG		3_prime_UTR_variant	5/5	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

Gnomad4 AFR exome AF: 0.0313

Gnomad4 AMR exome AF: 0.0765

Gnomad4 ASJ exome AF: 0.169

Gnomad4 EAS exome AF: 0.000793

Gnomad4 SAS exome AF: 0.0273

Gnomad4 FIN exome AF: 0.0830

Gnomad4 NFE exome AF: 0.110

Gnomad4 OTH exome AF: 0.102

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

Gnomad4 AFR AF: 0.0291

Gnomad4 AMR AF: 0.0899

Gnomad4 ASJ AF: 0.181

Gnomad4 EAS AF: 0.00251

Gnomad4 SAS AF: 0.0344

Gnomad4 FIN AF: 0.0856

Gnomad4 NFE AF: 0.115

Gnomad4 OTH AF: 0.120

Alfa AF: 0.0856 Hom.: 61

Bravo AF: 0.0820

Asia WGS AF: 0.0230 AC: 81 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 18, 2021

- -

Congenital generalized lipodystrophy Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

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: rs145169122; hg19: chr9-139567986;