9-136676978-G-T

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006412.4(AGPAT2):c.475C>A(p.Arg159Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000703 in 1,421,602 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict 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. R159L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

AGPAT2
NM_006412.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.85

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

congenital generalized lipodystrophy type 1
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
lipodystrophy
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
Berardinelli-Seip congenital lipodystrophy
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
neonatal diabetes mellitus
Inheritance: AR Classification: LIMITED Submitted by: Genomics England PanelApp

AGPAT2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.26091322).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006412.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGPAT2	NM_006412.4	MANE Select	c.475C>A	p.Arg159Ser	missense	Exon 3 of 6	NP_006403.2
	AGPAT2	NM_001012727.2		c.475C>A	p.Arg159Ser	missense	Exon 3 of 5	NP_001012745.1	O15120-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AGPAT2	ENST00000371696.7	TSL:1 MANE Select	c.475C>A	p.Arg159Ser	missense	Exon 3 of 6	ENSP00000360761.2	O15120-1
AGPAT2	ENST00000371694.7	TSL:1	c.475C>A	p.Arg159Ser	missense	Exon 3 of 5	ENSP00000360759.3	O15120-2
AGPAT2	ENST00000472820.1	TSL:1	n.403C>A		non_coding_transcript_exon	Exon 1 of 4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.03e-7

AC:

AN:

1421602

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

706974

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

32320

American (AMR)

AF:

0.00

AC:

AN:

43418

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24514

East Asian (EAS)

AF:

0.00

AC:

AN:

36672

South Asian (SAS)

AF:

0.00

AC:

AN:

85894

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49284

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5554

European-Non Finnish (NFE)

AF:

9.21e-7

AC:

AN:

1086362

Other (OTH)

AF:

0.00

AC:

AN:

57584

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.48

BayesDel_addAF

Uncertain

0.042

BayesDel_noAF

Benign

-0.18

CADD

Benign

(source)

DANN

Benign

0.83

DEOGEN2

Benign

0.30

Eigen

Benign

-0.38

Eigen_PC

Benign

-0.28

FATHMM_MKL

Benign

0.40

LIST_S2

Benign

0.70

M_CAP

Uncertain

0.17

MetaRNN

Benign

0.26

MetaSVM

Benign

-0.33

MutationAssessor

Benign

0.73

PhyloP100

2.9

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.28

REVEL

Benign

0.22

Sift

Benign

0.46

Sift4G

Benign

0.68

Polyphen

0.12

Vest4

0.34

MutPred

0.60

Loss of MoRF binding (P = 0.066)

MVP

0.95

MPC

0.28

ClinPred

0.26

GERP RS

2.7

Varity_R

0.38

gMVP

0.50

Mutation Taster

=90/10

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over