Genetic Variant DGAT2:p.Lys260Arg (chr11-75797302-A-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_032564.5(DGAT2):c.779A>G(p.Lys260Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000117 in 1,543,954 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

DGAT2
NM_032564.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.85

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:

UVRAG-DT (HGNC:):

UVRAG-DT links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High AC in GnomAdExome4 at 17 AD gene.

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.779A>G	p.Lys260Arg	missense	Exon 6 of 8	NP_115953.2
	DGAT2	NM_001253891.2		c.650A>G	p.Lys217Arg	missense	Exon 5 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.779A>G	p.Lys260Arg	missense	Exon 6 of 8	ENSP00000228027.6	Q96PD7-1
DGAT2	ENST00000376262.7	TSL:1	c.650A>G	p.Lys217Arg	missense	Exon 5 of 7	ENSP00000365438.3	Q96PD7-2
DGAT2	ENST00000604733.5	TSL:1	c.641A>G	p.Lys214Arg	missense	Exon 5 of 7	ENSP00000474668.1	S4R3S3

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000155

AC:

AN:

193062

AF XY:

0.0000193

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000122

AC:

AN:

1391752

Hom.:

Cov.:

AF XY:

0.0000116

AC XY:

AN XY:

688742

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30558

American (AMR)

AF:

0.000136

AC:

AN:

36808

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22834

East Asian (EAS)

AF:

0.00

AC:

AN:

35736

South Asian (SAS)

AF:

0.00

AC:

AN:

75550

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51338

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5434

European-Non Finnish (NFE)

AF:

0.0000111

AC:

AN:

1076232

Other (OTH)

AF:

0.00

AC:

AN:

57262

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.434

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152202

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41440

American (AMR)

AF:

0.00

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68028

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000378

ExAC

AF:

0.0000165

AC:

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.091

BayesDel_noAF

Benign

-0.14

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.23

Eigen

Uncertain

0.54

Eigen_PC

Uncertain

0.63

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.85

M_CAP

Benign

0.024

MetaRNN

Uncertain

0.63

MetaSVM

Benign

-1.2

MutationAssessor

Uncertain

2.4

PhyloP100

8.8

PrimateAI

Uncertain

0.74

PROVEAN

Uncertain

-2.4

REVEL

Benign

0.23

Sift

Benign

0.049

Sift4G

Benign

0.071

Polyphen

0.67

Vest4

0.89

MutPred

0.68

Gain of methylation at K260 (P = 0.0901)

MVP

0.68

MPC

0.39

ClinPred

0.49

GERP RS

6.0

Varity_R

0.65

gMVP

0.89

Mutation Taster

=37/63

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over