Genetic Variant DGAT2:p.Lys118Arg (chr11-75790290-A-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_032564.5(DGAT2):c.353A>G(p.Lys118Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K118T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

DGAT2
NM_032564.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.74

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

Charcot-Marie-Tooth disease
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

DGAT2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2209551).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032564.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DGAT2	NM_032564.5	MANE Select	c.353A>G	p.Lys118Arg	missense	Exon 3 of 8	NP_115953.2
	DGAT2	NM_001253891.2		c.224A>G	p.Lys75Arg	missense	Exon 2 of 7	NP_001240820.1	Q96PD7-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DGAT2	ENST00000228027.12	TSL:1 MANE Select	c.353A>G	p.Lys118Arg	missense	Exon 3 of 8	ENSP00000228027.6	Q96PD7-1
DGAT2	ENST00000376262.7	TSL:1	c.224A>G	p.Lys75Arg	missense	Exon 2 of 7	ENSP00000365438.3	Q96PD7-2
DGAT2	ENST00000604733.5	TSL:1	c.215A>G	p.Lys72Arg	missense	Exon 2 of 7	ENSP00000474668.1	S4R3S3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000399

AC:

AN:

250792

AF XY:

0.00000738

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000884

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.50

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.027

Eigen

Benign

-0.13

Eigen_PC

Benign

0.079

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.79

M_CAP

Benign

0.0086

MetaRNN

Benign

0.22

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.55

PhyloP100

4.7

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.45

REVEL

Benign

0.087

Sift

Benign

0.51

Sift4G

Benign

0.35

Polyphen

0.64

Vest4

0.39

MutPred

0.39

Loss of methylation at K118 (P = 0.0114)

MVP

0.64

MPC

0.11

ClinPred

0.39

GERP RS

5.6

Varity_R

0.11

gMVP

0.53

Mutation Taster

=80/20

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over