11-75797213-T-C

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_032564.5(DGAT2):c.690T>C(p.Ser230=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00712 in 1,572,188 control chromosomes in the GnomAD database, including 55 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0047 (6 hom., cov: 32)
  • Exomes 𝑓: 0.0074 (49 hom.)
• Consequence: DGAT2 NM_032564.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.03

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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP6: Variant 11-75797213-T-C is Benign according to our data. Variant chr11-75797213-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 708403.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-75797213-T-C is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-2.03 with no splicing effect.
• BS2: High Homozygotes in GnomAd at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DGAT2	NM_032564.5	c.690T>C	p.Ser230=	synonymous_variant	6/8	ENST00000228027.12
DGAT2	NM_001253891.2	c.561T>C	p.Ser187=	synonymous_variant	5/7
DGAT2	XM_011545304.3	c.600T>C	p.Ser200=	synonymous_variant	6/8
DGAT2	XM_047427716.1	c.417T>C	p.Ser139=	synonymous_variant	6/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DGAT2	ENST00000228027.12	c.690T>C	p.Ser230=	synonymous_variant	6/8	1	NM_032564.5	P1

Frequencies

GnomAD3 genomes AF: 0.00470 AC: 715 AN: 152000 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.00172

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00452

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00539

Gnomad FIN AF: 0.000661

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00760

Gnomad OTH AF: 0.00719

GnomAD3 exomes AF: 0.00456 AC: 996 AN: 218378 Hom.: 5 AF XY: 0.00481 AC XY: 570 AN XY: 118480

Gnomad AFR exome AF: 0.000977

Gnomad AMR exome AF: 0.00327

Gnomad ASJ exome AF: 0.00198

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00533

Gnomad FIN exome AF: 0.000674

Gnomad NFE exome AF: 0.00698

Gnomad OTH exome AF: 0.00395

GnomAD4 exome AF: 0.00738 AC: 10475 AN: 1420070 Hom.: 49 Cov.: 30 AF XY: 0.00735 AC XY: 5186 AN XY: 705212

Gnomad4 AFR exome AF: 0.00105

Gnomad4 AMR exome AF: 0.00356

Gnomad4 ASJ exome AF: 0.00179

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00527

Gnomad4 FIN exome AF: 0.00108

Gnomad4 NFE exome AF: 0.00851

Gnomad4 OTH exome AF: 0.00729

GnomAD4 genome AF: 0.00470 AC: 715 AN: 152118 Hom.: 6 Cov.: 32 AF XY: 0.00457 AC XY: 340 AN XY: 74380

Gnomad4 AFR AF: 0.00171

Gnomad4 AMR AF: 0.00452

Gnomad4 ASJ AF: 0.00202

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00560

Gnomad4 FIN AF: 0.000661

Gnomad4 NFE AF: 0.00760

Gnomad4 OTH AF: 0.00712

Alfa AF: 0.00601 Hom.: 1

Bravo AF: 0.00504

Asia WGS AF: 0.00375 AC: 13 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jul 26, 2018	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Apr 01, 2024	DGAT2: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
Cadd	Benign	7.5
Dann	Benign	0.66

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: rs143850439; hg19: chr11-75508258; COSMIC: COSV57176110; COSMIC: COSV57176110;