11-75720106-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_025098.4(MOGAT2):​c.206G>A​(p.Arg69Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000682 in 1,614,006 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

MOGAT2
NM_025098.4 missense

Scores

4
8
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.42
Variant links:
Genes affected
MOGAT2 (HGNC:23248): (monoacylglycerol O-acyltransferase 2) The protein encoded by this gene is an enzyme that catalyzes the synthesis of diacylglycerol from 2-monoacylglycerol and fatty acyl-CoA. The encoded protein is important in the uptake of dietary fat by the small intestine. This protein forms a complex with diacylglycerol O-acyltransferase 2 in the endoplasmic reticulum, and this complex catalyzes the synthesis of triacylglycerol. [provided by RefSeq, Dec 2015]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
MOGAT2NM_025098.4 linkuse as main transcriptc.206G>A p.Arg69Gln missense_variant 2/6 ENST00000198801.10 NP_079374.2
MOGAT2XM_011545267.2 linkuse as main transcriptc.206G>A p.Arg69Gln missense_variant 2/6 XP_011543569.1
MOGAT2XM_024448696.2 linkuse as main transcriptc.-41G>A 5_prime_UTR_variant 2/6 XP_024304464.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MOGAT2ENST00000198801.10 linkuse as main transcriptc.206G>A p.Arg69Gln missense_variant 2/61 NM_025098.4 ENSP00000198801 P1Q3SYC2-1
MOGAT2ENST00000526712.1 linkuse as main transcriptc.-41G>A 5_prime_UTR_variant 1/52 ENSP00000436283 Q3SYC2-2
MOGAT2ENST00000525093.5 linkuse as main transcriptc.206G>A p.Arg69Gln missense_variant, NMD_transcript_variant 2/52 ENSP00000436537 Q3SYC2-3

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152142
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.000576
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000796
AC:
2
AN:
251382
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135844
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:
0.00000880
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000616
AC:
9
AN:
1461864
Hom.:
0
Cov.:
31
AF XY:
0.00000825
AC XY:
6
AN XY:
727240
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000464
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.0000497
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152142
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74324
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.000576
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000434
Hom.:
0
Bravo
AF:
0.0000113
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.00000824
AC:
1
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJan 02, 2024The c.206G>A (p.R69Q) alteration is located in exon 2 (coding exon 2) of the MOGAT2 gene. This alteration results from a G to A substitution at nucleotide position 206, causing the arginine (R) at amino acid position 69 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.18
BayesDel_addAF
Uncertain
0.12
D
BayesDel_noAF
Uncertain
0.030
CADD
Pathogenic
31
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.19
T
Eigen
Pathogenic
0.85
Eigen_PC
Pathogenic
0.71
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Benign
0.85
D
M_CAP
Benign
0.061
D
MetaRNN
Uncertain
0.71
D
MetaSVM
Benign
-0.41
T
MutationAssessor
Pathogenic
3.8
H
MutationTaster
Benign
1.0
D;D
PrimateAI
Benign
0.33
T
PROVEAN
Uncertain
-3.2
D
REVEL
Uncertain
0.37
Sift
Uncertain
0.0010
D
Sift4G
Uncertain
0.0050
D
Polyphen
1.0
D
Vest4
0.57
MVP
0.59
MPC
0.55
ClinPred
1.0
D
GERP RS
5.0
Varity_R
0.85
gMVP
0.81

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.

Other links and lift over

dbSNP: rs369433013; hg19: chr11-75431151; API