Genetic Variant DGAT2:p.Gly250Asp (chr11-75797272-G-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2

The NM_032564.5(DGAT2):c.749G>A(p.Gly250Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00137 in 1,574,470 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0011 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0014 ( 2 hom. )

Consequence

DGAT2
NM_032564.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 9.49

Variant links:

Genes affected

DGAT2 (HGNC:16940): (diacylglycerol O-acyltransferase 2) This gene encodes one of two enzymes which catalyzes the final reaction in the synthesis of triglycerides in which diacylglycerol is covalently bound to long chain fatty acyl-CoAs. The encoded protein catalyzes this reaction at low concentrations of magnesium chloride while the other enzyme has high activity at high concentrations of magnesium chloride. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

DGAT2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.068149924).

BP6

Variant 11-75797272-G-A is Benign according to our data. Variant chr11-75797272-G-A is described in ClinVar as [Benign]. Clinvar id is 2642161.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DGAT2	NM_032564.5 link	c.749G>A	p.Gly250Asp	missense_variant	Exon 6 of 8	ENST00000228027.12	NP_115953.2	Q96PD7-1
DGAT2	NM_001253891.2 link	c.620G>A	p.Gly207Asp	missense_variant	Exon 5 of 7		NP_001240820.1	Q96PD7-2
DGAT2	XM_011545304.3 link	c.659G>A	p.Gly220Asp	missense_variant	Exon 6 of 8		XP_011543606.1
DGAT2	XM_047427716.1 link	c.476G>A	p.Gly159Asp	missense_variant	Exon 6 of 8		XP_047283672.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DGAT2	ENST00000228027.12 link	c.749G>A	p.Gly250Asp	missense_variant	Exon 6 of 8	1	NM_032564.5	ENSP00000228027.6		Q96PD7-1

Frequencies

GnomAD3 genomes

AF:

0.00114

AC:

173

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000362

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00249

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000471

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00166

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00115

AC:

250

AN:

216904

Hom.:

AF XY:

0.00111

AC XY:

131

AN XY:

117740

show subpopulations

Gnomad AFR exome

AF:

0.000279

Gnomad AMR exome

AF:

0.00121

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000353

Gnomad FIN exome

AF:

0.00135

Gnomad NFE exome

AF:

0.00173

Gnomad OTH exome

AF:

0.000399

GnomAD4 exome

AF:

0.00140

AC:

1985

AN:

1422174

Hom.:

Cov.:

AF XY:

0.00140

AC XY:

987

AN XY:

706590

show subpopulations

Gnomad4 AFR exome

AF:

0.000128

Gnomad4 AMR exome

AF:

0.00142

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000544

Gnomad4 FIN exome

AF:

0.000684

Gnomad4 NFE exome

AF:

0.00161

Gnomad4 OTH exome

AF:

0.00123

GnomAD4 genome

AF:

0.00114

AC:

173

AN:

152296

Hom.:

Cov.:

AF XY:

0.00102

AC XY:

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.000361

Gnomad4 AMR

AF:

0.00248

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.000471

Gnomad4 NFE

AF:

0.00166

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00149

Hom.:

Bravo

AF:

0.00139

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.00285

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00186

AC:

ExAC

AF:

0.00121

AC:

147

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Feb 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

DGAT2: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.43

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Uncertain

0.020

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.24

.;T;.;.

Eigen

Pathogenic

0.93

Eigen_PC

Pathogenic

0.93

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.86

D;D;D;D

M_CAP

Benign

0.031

MetaRNN

Benign

0.068

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.8

.;M;.;.

PrimateAI

Uncertain

0.71

PROVEAN

Pathogenic

-5.6

.;D;D;.

REVEL

Uncertain

0.53

Sift

Uncertain

0.010

.;D;D;.

Sift4G

Pathogenic

0.0

D;D;D;D

Polyphen

1.0

.;D;D;.

Vest4

0.91, 0.89

MVP

0.79

MPC

0.64

ClinPred

0.080

GERP RS

6.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.91

gMVP

0.88

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