Variant rs200656731 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_006412.4(AGPAT2):c.713C>T(p.Ala238Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000549 in 1,602,824 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000054 ( 0 hom. )

Consequence

AGPAT2
NM_006412.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.125

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.018196613).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AGPAT2	NM_006412.4 linkuse as main transcript	c.713C>T	p.Ala238Val	missense_variant	6/6	ENST00000371696.7	NP_006403.2	O15120-1A0A024R8I7
AGPAT2	NM_001012727.2 linkuse as main transcript	c.617C>T	p.Ala206Val	missense_variant	5/5		NP_001012745.1	O15120-2A0A024R8F9
AGPAT2	XM_047422636.1 linkuse as main transcript	c.404C>T	p.Ala135Val	missense_variant	6/6		XP_047278592.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
AGPAT2	ENST00000371696.7 linkuse as main transcript	c.713C>T	p.Ala238Val	missense_variant	6/6	1	NM_006412.4	ENSP00000360761.2	O15120-1
AGPAT2	ENST00000371694.7 linkuse as main transcript	c.617C>T	p.Ala206Val	missense_variant	5/5	1		ENSP00000360759.3	O15120-2
AGPAT2	ENST00000472820.1 linkuse as main transcript	n.641C>T		non_coding_transcript_exon_variant	4/4	1

Frequencies

GnomAD3 genomes

AF:

0.0000657

AC:

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000729

AC:

AN:

233076

Hom.:

AF XY:

0.0000552

AC XY:

AN XY:

126712

show subpopulations

Gnomad AFR exome

AF:

0.0000676

Gnomad AMR exome

AF:

0.0000613

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000171

Gnomad SAS exome

AF:

0.000105

Gnomad FIN exome

AF:

0.0000511

Gnomad NFE exome

AF:

0.0000668

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000538

AC:

AN:

1450518

Hom.:

Cov.:

AF XY:

0.0000499

AC XY:

AN XY:

720936

show subpopulations

Gnomad4 AFR exome

AF:

0.0000601

Gnomad4 AMR exome

AF:

0.0000458

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000509

Gnomad4 SAS exome

AF:

0.0000829

Gnomad4 FIN exome

AF:

0.0000193

Gnomad4 NFE exome

AF:

0.0000542

Gnomad4 OTH exome

AF:

0.0000669

GnomAD4 genome

AF:

0.0000657

AC:

AN:

152306

Hom.:

Cov.:

AF XY:

0.0000806

AC XY:

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.0000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000387

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000127

Hom.:

Bravo

AF:

0.0000680

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000580

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Congenital generalized lipodystrophy type 1

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Jun 17, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.42

CADD

Benign

0.18

DANN

Benign

0.71

DEOGEN2

Benign

0.072

.;T;T

Eigen

Benign

-2.0

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.42

LIST_S2

Benign

0.094

T;.;T

M_CAP

Uncertain

0.24

MetaRNN

Benign

0.018

T;T;T

MetaSVM

Benign

-0.57

MutationAssessor

Benign

-0.51

.;N;N

PrimateAI

Benign

0.34

PROVEAN

Benign

0.16

N;N;N

REVEL

Benign

0.21

Sift

Benign

0.71

T;T;T

Sift4G

Benign

0.33

T;T;T

Polyphen

0.0010

B;B;B

Vest4

0.029

MVP

0.66

MPC

0.16

ClinPred

0.011

GERP RS

-4.6

Varity_R

0.024

gMVP

0.26

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