Variant 9-136677108-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_006412.4(AGPAT2):c.345C>G(p.Cys115Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,826 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

AGPAT2
NM_006412.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.156

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.98

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AGPAT2	NM_006412.4 linkuse as main transcript	c.345C>G	p.Cys115Trp	missense_variant	3/6	ENST00000371696.7	NP_006403.2	O15120-1A0A024R8I7
AGPAT2	NM_001012727.2 linkuse as main transcript	c.345C>G	p.Cys115Trp	missense_variant	3/5		NP_001012745.1	O15120-2A0A024R8F9
AGPAT2	XM_047422636.1 linkuse as main transcript	c.36C>G	p.Cys12Trp	missense_variant	3/6		XP_047278592.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
AGPAT2	ENST00000371696.7 linkuse as main transcript	c.345C>G	p.Cys115Trp	missense_variant	3/6	1	NM_006412.4	ENSP00000360761.2	O15120-1
AGPAT2	ENST00000371694.7 linkuse as main transcript	c.345C>G	p.Cys115Trp	missense_variant	3/5	1		ENSP00000360759.3	O15120-2
AGPAT2	ENST00000472820.1 linkuse as main transcript	n.273C>G		non_coding_transcript_exon_variant	1/4	1
AGPAT2	ENST00000470861.1 linkuse as main transcript	n.639C>G		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000403

AC:

AN:

247990

Hom.:

AF XY:

0.00000743

AC XY:

AN XY:

134674

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460826

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726710

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.99

BayesDel_addAF

Pathogenic

0.36

BayesDel_noAF

Pathogenic

0.38

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Pathogenic

0.82

.;D;D

Eigen

Benign

-0.32

Eigen_PC

Benign

-0.51

FATHMM_MKL

Benign

0.65

LIST_S2

Uncertain

0.87

D;.;D

M_CAP

Pathogenic

0.84

MetaRNN

Pathogenic

0.98

D;D;D

MetaSVM

Uncertain

0.61

MutationAssessor

Pathogenic

3.0

M;M;M

PrimateAI

Uncertain

0.76

PROVEAN

Pathogenic

-11

D;D;D

REVEL

Pathogenic

0.73

Sift

Pathogenic

0.0

D;D;D

Sift4G

Pathogenic

0.0010

D;D;D

Polyphen

1.0

D;D;D

Vest4

0.86

MutPred

0.73

Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);

MVP

0.97

MPC

0.78

ClinPred

1.0

GERP RS

-3.2

Varity_R

0.95

gMVP

0.95

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over