rs142993240

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_006412.4(AGPAT2):c.475C>T(p.Arg159Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00516 in 1,570,472 control chromosomes in the GnomAD database, including 36 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). 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: 𝑓 0.0045 ( 6 hom., cov: 32)

Exomes 𝑓: 0.0052 ( 30 hom. )

Consequence

AGPAT2
NM_006412.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts U:1B:9O:1

Conservation

PhyloP100: 2.85

Publications

13 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: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.013234198).

BP6

Variant 9-136676978-G-A is Benign according to our data. Variant chr9-136676978-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 210105.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00451 (671/148876) while in subpopulation SAS AF = 0.00814 (37/4548). AF 95% confidence interval is 0.00607. There are 6 homozygotes in GnomAd4. There are 327 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 6 AR gene

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>T	p.Arg159Cys	missense	Exon 3 of 6	NP_006403.2
	AGPAT2	NM_001012727.2		c.475C>T	p.Arg159Cys	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>T	p.Arg159Cys	missense	Exon 3 of 6	ENSP00000360761.2	O15120-1
AGPAT2	ENST00000371694.7	TSL:1	c.475C>T	p.Arg159Cys	missense	Exon 3 of 5	ENSP00000360759.3	O15120-2
AGPAT2	ENST00000472820.1	TSL:1	n.403C>T		non_coding_transcript_exon	Exon 1 of 4

Frequencies

GnomAD3 genomes

AF:

0.00451

AC:

671

AN:

148742

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00141

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00568

Gnomad ASJ

AF:

0.0102

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00814

Gnomad FIN

AF:

0.00142

Gnomad MID

AF:

0.0255

Gnomad NFE

AF:

0.00621

Gnomad OTH

AF:

0.00824

GnomAD2 exomes

AF:

0.00514

AC:

1277

AN:

248240

AF XY:

0.00561

show subpopulations

Gnomad AFR exome

AF:

0.000557

Gnomad AMR exome

AF:

0.00498

Gnomad ASJ exome

AF:

0.0101

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00134

Gnomad NFE exome

AF:

0.00624

Gnomad OTH exome

AF:

0.00918

GnomAD4 exome

AF:

0.00523

AC:

7438

AN:

1421596

Hom.:

Cov.:

AF XY:

0.00541

AC XY:

3823

AN XY:

706970

show subpopulations

African (AFR)

AF:

0.000897

AC:

AN:

32320

American (AMR)

AF:

0.00525

AC:

228

AN:

43418

Ashkenazi Jewish (ASJ)

AF:

0.0113

AC:

278

AN:

24514

East Asian (EAS)

AF:

0.00

AC:

AN:

36672

South Asian (SAS)

AF:

0.00745

AC:

640

AN:

85894

European-Finnish (FIN)

AF:

0.00207

AC:

102

AN:

49284

Middle Eastern (MID)

AF:

0.0200

AC:

111

AN:

5554

European-Non Finnish (NFE)

AF:

0.00524

AC:

5691

AN:

1086356

Other (OTH)

AF:

0.00623

AC:

359

AN:

57584

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

433

867

1300

1734

2167

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

200

400

600

800

1000

<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

AF:

0.00451

AC:

671

AN:

148876

Hom.:

Cov.:

AF XY:

0.00450

AC XY:

327

AN XY:

72600

show subpopulations

African (AFR)

AF:

0.00140

AC:

AN:

40594

American (AMR)

AF:

0.00567

AC:

AN:

14980

Ashkenazi Jewish (ASJ)

AF:

0.0102

AC:

AN:

3438

East Asian (EAS)

AF:

0.00

AC:

AN:

4856

South Asian (SAS)

AF:

0.00814

AC:

AN:

4548

European-Finnish (FIN)

AF:

0.00142

AC:

AN:

9860

Middle Eastern (MID)

AF:

0.0274

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00621

AC:

418

AN:

67330

Other (OTH)

AF:

0.00815

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

126

157

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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

Alfa

AF:

0.00599

Hom.:

Bravo

AF:

0.00459

TwinsUK

AF:

0.00485

AC:

ALSPAC

AF:

0.00363

AC:

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.00558

AC:

ExAC

AF:

0.00545

AC:

661

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (4)

not specified (3)

Congenital generalized lipodystrophy type 1 (2)

AGPAT2-related disorder (1)

Monogenic diabetes (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.12

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.63

Eigen

Uncertain

0.39

Eigen_PC

Uncertain

0.28

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.84

M_CAP

Pathogenic

0.38

MetaRNN

Benign

0.013

MetaSVM

Uncertain

0.56

MutationAssessor

Benign

1.9

PhyloP100

2.9

PrimateAI

Benign

0.30

PROVEAN

Benign

-1.3

REVEL

Uncertain

0.58

Sift

Benign

0.040

Sift4G

Benign

0.13

Polyphen

0.99

Vest4

0.33

MVP

0.99

MPC

0.68

ClinPred

0.015

GERP RS

2.7

Varity_R

0.28

gMVP

0.55

Mutation Taster

=96/4

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over