Variant 9-136677531-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_006412.4(AGPAT2):c.208T>C(p.Phe70Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,538 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. F70V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

AGPAT2
NM_006412.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.73

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.26880807).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
AGPAT2	NM_006412.4 linkuse as main transcript	c.208T>C	p.Phe70Leu	missense_variant	2/6	ENST00000371696.7
AGPAT2	NM_001012727.2 linkuse as main transcript	c.208T>C	p.Phe70Leu	missense_variant	2/5
AGPAT2	XM_047422636.1 linkuse as main transcript	c.-102T>C		5_prime_UTR_variant	2/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AGPAT2	ENST00000371696.7 linkuse as main transcript	c.208T>C	p.Phe70Leu	missense_variant	2/6	1	NM_006412.4	P1	O15120-1
AGPAT2	ENST00000371694.7 linkuse as main transcript	c.208T>C	p.Phe70Leu	missense_variant	2/5	1			O15120-2
AGPAT2	ENST00000470861.1 linkuse as main transcript	n.216T>C		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000403

AC:

AN:

248162

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135044

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

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:

0.00

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460538

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726590

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000825

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.87

BayesDel_addAF

Uncertain

0.026

BayesDel_noAF

Benign

-0.12

CADD

Benign

DANN

Benign

0.91

Eigen

Benign

-0.35

Eigen_PC

Benign

-0.18

FATHMM_MKL

Benign

0.72

LIST_S2

Benign

0.74

T;.;T

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.27

T;T;T

MetaSVM

Uncertain

-0.18

MutationAssessor

Benign

1.7

L;L;L

MutationTaster

Benign

0.97

D;D;D

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-1.0

N;N;N

REVEL

Uncertain

0.33

Sift

Benign

0.79

T;T;T

Sift4G

Benign

0.63

T;T;T

Polyphen

0.0010

B;B;B

Vest4

0.36

MutPred

0.45

Loss of methylation at K71 (P = 0.1214);Loss of methylation at K71 (P = 0.1214);Loss of methylation at K71 (P = 0.1214);

MVP

0.97

MPC

0.18

ClinPred

0.21

GERP RS

4.5

Varity_R

0.12

gMVP

0.65

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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