9-136676697-G-T

Position:

chr9-136676697-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_006412.4(AGPAT2):c.493-17C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000484 in 1,610,610 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0026 ( 2 hom., cov: 33)

Exomes 𝑓: 0.00026 ( 1 hom. )

Consequence

AGPAT2
NM_006412.4 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.228

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:

AGPAT2 (HGNC:):

AGPAT2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 9-136676697-G-T is Benign according to our data. Variant chr9-136676697-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 259978.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0026 (396/152282) while in subpopulation AFR AF= 0.00912 (379/41578). AF 95% confidence interval is 0.00836. There are 2 homozygotes in gnomad4. There are 182 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
AGPAT2	NM_006412.4 linkuse as main transcript	c.493-17C>A	intron_variant	ENST00000371696.7	NP_006403.2	O15120-1A0A024R8I7
AGPAT2	NM_001012727.2 linkuse as main transcript	c.492+264C>A	intron_variant		NP_001012745.1	O15120-2A0A024R8F9
AGPAT2	XM_047422636.1 linkuse as main transcript	c.184-17C>A	intron_variant		XP_047278592.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
AGPAT2	ENST00000371696.7 linkuse as main transcript	c.493-17C>A	intron_variant	1	NM_006412.4	ENSP00000360761.2	O15120-1
AGPAT2	ENST00000371694.7 linkuse as main transcript	c.492+264C>A	intron_variant	1		ENSP00000360759.3	O15120-2
AGPAT2	ENST00000472820.1 linkuse as main transcript	n.421-17C>A	intron_variant	1

Frequencies

GnomAD3 genomes

AF:

0.00260

AC:

395

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00912

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000589

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00336

GnomAD3 exomes

AF:

0.000671

AC:

168

AN:

250188

Hom.:

AF XY:

0.000487

AC XY:

AN XY:

135650

show subpopulations

Gnomad AFR exome

AF:

0.00897

Gnomad AMR exome

AF:

0.000608

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000327

GnomAD4 exome

AF:

0.000263

AC:

383

AN:

1458328

Hom.:

Cov.:

AF XY:

0.000243

AC XY:

176

AN XY:

725706

show subpopulations

Gnomad4 AFR exome

AF:

0.00949

Gnomad4 AMR exome

AF:

0.000649

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000541

Gnomad4 OTH exome

AF:

0.000448

GnomAD4 genome

AF:

0.00260

AC:

396

AN:

152282

Hom.:

Cov.:

AF XY:

0.00244

AC XY:

182

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.00912

Gnomad4 AMR

AF:

0.000588

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00333

Bravo

AF:

0.00280

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Aug 31, 2023	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Congenital generalized lipodystrophy type 1

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Jul 23, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

1.4

DANN

Benign

0.71

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

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