11-75720105-C-T

Variant names:

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_025098.4(MOGAT2):c.205C>T(p.Arg69Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000167 in 1,613,976 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R69Q) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

MOGAT2
NM_025098.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.440

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]

MOGAT2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.935

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MOGAT2	NM_025098.4 link	c.205C>T	p.Arg69Trp	missense_variant	Exon 2 of 6	ENST00000198801.10	NP_079374.2	Q3SYC2-1
MOGAT2	XM_024448696.2 link	c.-42C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 2 of 6		XP_024304464.1
MOGAT2	XM_011545267.2 link	c.205C>T	p.Arg69Trp	missense_variant	Exon 2 of 6		XP_011543569.1
MOGAT2	XM_024448696.2 link	c.-42C>T		5_prime_UTR_variant	Exon 2 of 6		XP_024304464.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MOGAT2	ENST00000198801.10 link	c.205C>T	p.Arg69Trp	missense_variant	Exon 2 of 6	1	NM_025098.4	ENSP00000198801.5	Q3SYC2-1
MOGAT2	ENST00000526712 link	c.-42C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 5	2		ENSP00000436283.1	Q3SYC2-2
MOGAT2	ENST00000526712 link	c.-42C>T		5_prime_UTR_variant	Exon 1 of 5	2		ENSP00000436283.1	Q3SYC2-2
MOGAT2	ENST00000525093.5 link	n.205C>T		non_coding_transcript_exon_variant	Exon 2 of 5	2		ENSP00000436537.1	Q3SYC2-3

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152106

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000438

AC:

AN:

251382

Hom.:

AF XY:

0.0000515

AC XY:

AN XY:

135840

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.000202

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:

0.0000176

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000164

AC:

AN:

1461870

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000201

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:

0.0000117

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152106

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74296

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.0000378

ExAC

AF:

0.0000494

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 19, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.205C>T (p.R69W) alteration is located in exon 2 (coding exon 2) of the MOGAT2 gene. This alteration results from a C to T substitution at nucleotide position 205, causing the arginine (R) at amino acid position 69 to be replaced by a tryptophan (W). 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

0.20

BayesDel_addAF

Benign

-0.010

BayesDel_noAF

Uncertain

0.030

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.23

Eigen

Benign

0.052

Eigen_PC

Benign

-0.14

FATHMM_MKL

Benign

0.60

LIST_S2

Uncertain

0.88

M_CAP

Uncertain

0.12

MetaRNN

Pathogenic

0.94

MetaSVM

Benign

-0.57

MutationAssessor

Pathogenic

4.1

PrimateAI

Benign

0.39

PROVEAN

Pathogenic

-6.7

REVEL

Uncertain

0.41

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0010

Polyphen

0.95

Vest4

0.88

MutPred

0.73

Loss of disorder (P = 0.0042);

MVP

0.44

MPC

0.54

ClinPred

0.95

GERP RS

2.7

Varity_R

0.75

gMVP

0.86

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over