9-136677143-G-A

Position:

chr9-136677143-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006412.4(AGPAT2):c.317-7C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00303 in 1,612,570 control chromosomes in the GnomAD database, including 148 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.016 ( 71 hom., cov: 33)

Exomes 𝑓: 0.0016 ( 77 hom. )

Consequence

AGPAT2
NM_006412.4 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.001413

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.706

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 9-136677143-G-A is Benign according to our data. Variant chr9-136677143-G-A is described in ClinVar as [Benign]. Clinvar id is 128288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0543 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
AGPAT2	NM_006412.4 linkuse as main transcript	c.317-7C>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	ENST00000371696.7	NP_006403.2
AGPAT2	NM_001012727.2 linkuse as main transcript	c.317-7C>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		NP_001012745.1
AGPAT2	XM_047422636.1 linkuse as main transcript	c.8-7C>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		XP_047278592.1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AGPAT2	ENST00000371696.7 linkuse as main transcript	c.317-7C>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_006412.4	ENSP00000360761	P1	O15120-1
AGPAT2	ENST00000371694.7 linkuse as main transcript	c.317-7C>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1		ENSP00000360759		O15120-2
AGPAT2	ENST00000472820.1 linkuse as main transcript	n.238C>T	non_coding_transcript_exon_variant	1/4	1
AGPAT2	ENST00000470861.1 linkuse as main transcript	n.604C>T	non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

AF:

0.0162

AC:

2472

AN:

152244

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0563

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00661

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000220

Gnomad OTH

AF:

0.0100

GnomAD3 exomes

AF:

0.00411

AC:

1010

AN:

245834

Hom.:

AF XY:

0.00308

AC XY:

413

AN XY:

134006

show subpopulations

Gnomad AFR exome

AF:

0.0568

Gnomad AMR exome

AF:

0.00273

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000654

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000458

Gnomad OTH exome

AF:

0.00214

GnomAD4 exome

AF:

0.00165

AC:

2407

AN:

1460208

Hom.:

Cov.:

AF XY:

0.00144

AC XY:

1045

AN XY:

726380

show subpopulations

Gnomad4 AFR exome

AF:

0.0599

Gnomad4 AMR exome

AF:

0.00338

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000270

Gnomad4 OTH exome

AF:

0.00350

GnomAD4 genome

AF:

0.0162

AC:

2475

AN:

152362

Hom.:

Cov.:

AF XY:

0.0156

AC XY:

1159

AN XY:

74512

show subpopulations

Gnomad4 AFR

AF:

0.0562

Gnomad4 AMR

AF:

0.00660

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000220

Gnomad4 OTH

AF:

0.00993

Alfa

AF:

0.00631

Hom.:

Bravo

AF:

0.0191

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 05, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 28, 2024	- -

Congenital generalized lipodystrophy type 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

0.33

DANN

Benign

0.87

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0014

dbscSNV1_RF

Benign

0.036

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over