Genetic Variant NM_032564.5:c.802C>T (chr11-75797325-C-T) – 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.802C>T(p.Arg268Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000776 in 1,495,790 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000082 ( 0 hom. )

Consequence

DGAT2
NM_032564.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.42

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 GnomAd4 at 6 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.802C>T	p.Arg268Cys	missense	Exon 6 of 8	NP_115953.2
	DGAT2	NM_001253891.2		c.673C>T	p.Arg225Cys	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.802C>T	p.Arg268Cys	missense	Exon 6 of 8	ENSP00000228027.6	Q96PD7-1
DGAT2	ENST00000376262.7	TSL:1	c.673C>T	p.Arg225Cys	missense	Exon 5 of 7	ENSP00000365438.3	Q96PD7-2
DGAT2	ENST00000604733.5	TSL:1	c.664C>T	p.Arg222Cys	missense	Exon 5 of 7	ENSP00000474668.1	S4R3S3

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000368

AC:

AN:

162888

AF XY:

0.0000230

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:

0.0000774

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000819

AC:

110

AN:

1343578

Hom.:

Cov.:

AF XY:

0.0000878

AC XY:

AN XY:

660476

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

28968

American (AMR)

AF:

0.00

AC:

AN:

32034

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20762

East Asian (EAS)

AF:

0.00

AC:

AN:

33990

South Asian (SAS)

AF:

0.0000583

AC:

AN:

68640

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48902

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5044

European-Non Finnish (NFE)

AF:

0.0000924

AC:

AN:

1050244

Other (OTH)

AF:

0.000164

AC:

AN:

54994

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

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:

0.0000394

AC:

AN:

152212

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41448

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:

5196

South Asian (SAS)

AF:

0.000207

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000735

AC:

AN:

68032

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

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:

0.00

Hom.:

Bravo

AF:

0.0000529

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.0000249

AC:

ClinVar

ClinVar submissions

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

0.13

BayesDel_addAF

Benign

-0.072

BayesDel_noAF

Benign

-0.34

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.32

Eigen

Pathogenic

0.69

Eigen_PC

Pathogenic

0.68

FATHMM_MKL

Uncertain

0.79

LIST_S2

Pathogenic

0.98

M_CAP

Benign

0.022

MetaRNN

Uncertain

0.46

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.1

PhyloP100

2.4

PrimateAI

Benign

0.44

PROVEAN

Pathogenic

-4.9

REVEL

Benign

0.19

Sift

Uncertain

0.0040

Sift4G

Uncertain

0.012

Polyphen

1.0

Vest4

0.59

MVP

0.60

MPC

0.55

ClinPred

0.72

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.78

gMVP

0.71

Mutation Taster

=67/33

polymorphism

(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.

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