Genetic Variant NM_032564.5:c.690T>C (chr11-75797213-T-C) – ACMG Classification: Benign (-17 pts)

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_032564.5(DGAT2):c.690T>C(p.Ser230Ser) 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

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -2.03

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 -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 GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DGAT2	NM_032564.5 link	c.690T>C	p.Ser230Ser	synonymous_variant	Exon 6 of 8	ENST00000228027.12	NP_115953.2	Q96PD7-1
DGAT2	NM_001253891.2 link	c.561T>C	p.Ser187Ser	synonymous_variant	Exon 5 of 7		NP_001240820.1	Q96PD7-2
DGAT2	XM_011545304.3 link	c.600T>C	p.Ser200Ser	synonymous_variant	Exon 6 of 8		XP_011543606.1
DGAT2	XM_047427716.1 link	c.417T>C	p.Ser139Ser	synonymous_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.690T>C	p.Ser230Ser	synonymous_variant	Exon 6 of 8	1	NM_032564.5	ENSP00000228027.6		Q96PD7-1

Frequencies

GnomAD3 genomes

AF:

0.00470

AC:

715

AN:

152000

Hom.:

Cov.:

show subpopulations

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.:

AF XY:

0.00481

AC XY:

570

AN XY:

118480

show subpopulations

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.:

Cov.:

AF XY:

0.00735

AC XY:

5186

AN XY:

705212

show subpopulations

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.:

Cov.:

AF XY:

0.00457

AC XY:

340

AN XY:

74380

show subpopulations

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.:

Bravo

AF:

0.00504

Asia WGS

AF:

0.00375

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Jun 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

DGAT2: BP4, BP7, BS2 -

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 26, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

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