Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The ENST00000228027.12(DGAT2):c.667T>C(p.Tyr223His) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Y223S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

DGAT2
ENST00000228027.12 missense

Scores

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 5.87

Publications

8 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:

UVRAG-DT (HGNC:):

UVRAG-DT links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000228027.12. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DGAT2	NM_032564.5	MANE Select	c.667T>C	p.Tyr223His	missense	Exon 6 of 8	NP_115953.2
	DGAT2	NM_001253891.2		c.538T>C	p.Tyr180His	missense	Exon 5 of 7	NP_001240820.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
DGAT2	ENST00000228027.12	TSL:1 MANE Select	c.667T>C	p.Tyr223His	missense	Exon 6 of 8	ENSP00000228027.6
DGAT2	ENST00000376262.7	TSL:1	c.538T>C	p.Tyr180His	missense	Exon 5 of 7	ENSP00000365438.3
DGAT2	ENST00000604733.5	TSL:1	c.529T>C	p.Tyr177His	missense	Exon 5 of 7	ENSP00000474668.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1396898

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

691264

African (AFR)

AF:

0.00

AC:

AN:

30792

American (AMR)

AF:

0.00

AC:

AN:

38090

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23356

East Asian (EAS)

AF:

0.00

AC:

AN:

35676

South Asian (SAS)

AF:

0.00

AC:

AN:

76804

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51846

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5504

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1077326

Other (OTH)

AF:

0.00

AC:

AN:

57504

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Uncertain

0.086

BayesDel_noAF

Benign

-0.11

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.14

Eigen

Benign

0.016

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Uncertain

0.89

LIST_S2

Uncertain

0.91

M_CAP

Benign

0.011

MetaRNN

Uncertain

0.51

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.3

PhyloP100

5.9

PrimateAI

Pathogenic

0.80

PROVEAN

Uncertain

-2.6

REVEL

Benign

0.20

Sift

Benign

0.43

Sift4G

Benign

0.49

Polyphen

0.026

Vest4

0.55

MutPred

0.65

Gain of disorder (P = 0.0281)

MVP

0.41

MPC

0.24

ClinPred

0.80

GERP RS

6.0

Varity_R

0.41

gMVP

0.80

Mutation Taster

=3/97

disease causing

(source)

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

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

rs869025595

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over