11-75798307-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_032564.5(DGAT2):c.890G>A(p.Arg297Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00291 in 1,614,168 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0022 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0030 (10 hom.)
• Consequence: DGAT2 NM_032564.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:3
• Conservation: PhyloP100: 6.41

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.011948973).
• BP6: Variant 11-75798307-G-A is Benign according to our data. Variant chr11-75798307-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1284806.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-75798307-G-A is described in Lovd as [Likely_benign].
• BS2: High Homozygotes in GnomAdExome at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DGAT2	NM_032564.5	c.890G>A	p.Arg297Gln	missense_variant	7/8	ENST00000228027.12
DGAT2	NM_001253891.2	c.761G>A	p.Arg254Gln	missense_variant	6/7
DGAT2	XM_011545304.3	c.800G>A	p.Arg267Gln	missense_variant	7/8
DGAT2	XM_047427716.1	c.617G>A	p.Arg206Gln	missense_variant	7/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DGAT2	ENST00000228027.12	c.890G>A	p.Arg297Gln	missense_variant	7/8	1	NM_032564.5	P1

Frequencies

GnomAD3 genomes AF: 0.00216 AC: 329 AN: 152174 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00174

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00164

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00186

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00319

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.00230 AC: 579 AN: 251402 Hom.: 2 AF XY: 0.00231 AC XY: 314 AN XY: 135864

Gnomad AFR exome AF: 0.00172

Gnomad AMR exome AF: 0.000838

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.00252

Gnomad FIN exome AF: 0.000601

Gnomad NFE exome AF: 0.00367

Gnomad OTH exome AF: 0.00212

GnomAD4 exome AF: 0.00298 AC: 4362 AN: 1461876 Hom.: 10 Cov.: 31 AF XY: 0.00287 AC XY: 2089 AN XY: 727242

Gnomad4 AFR exome AF: 0.00131

Gnomad4 AMR exome AF: 0.00103

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00206

Gnomad4 FIN exome AF: 0.00105

Gnomad4 NFE exome AF: 0.00351

Gnomad4 OTH exome AF: 0.00215

GnomAD4 genome AF: 0.00216 AC: 329 AN: 152292 Hom.: 1 Cov.: 32 AF XY: 0.00201 AC XY: 150 AN XY: 74458

Gnomad4 AFR AF: 0.00173

Gnomad4 AMR AF: 0.00163

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00187

Gnomad4 FIN AF: 0.000188

Gnomad4 NFE AF: 0.00319

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.00256 Hom.: 2

Bravo AF: 0.00223

TwinsUK AF: 0.00378 AC: 14

ALSPAC AF: 0.00259 AC: 10

ESP6500AA AF: 0.00273 AC: 12

ESP6500EA AF: 0.00314 AC: 27

ExAC AF: 0.00261 AC: 317

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00229

EpiControl AF: 0.00338

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:3

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Oct 01, 2023	DGAT2: BS2 -
Likely benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Uncertain	-0.070
Cadd	Uncertain	25
Dann	Pathogenic	1.0
DEOGEN2	Benign	0.18	T;.;.
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.93	D;D;D
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.012	T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.5	M;.;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-2.3	N;N;.
REVEL	Benign	0.29
Sift	Uncertain	0.021	D;D;.
Sift4G	Uncertain	0.049	D;T;T
Polyphen		0.93	P;P;.
Vest4		0.81
MVP		0.53
MPC		0.57
ClinPred		0.057	T
GERP RS		3.6
Varity_R		0.28
gMVP		0.84

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs140793537; hg19: chr11-75509352; COSMIC: COSV99930109; COSMIC: COSV99930109;