rs772143127

Variant names:

• chr11-75797302-A-G
• rs772143127
• NM_032564.5:c.779A>G

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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.85
• Publications: 0 publications found

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

UVRAG-DT (HGNC:):

ACMG classification

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

Sel.	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: 1 AN: 152202 Hom.: 0 Cov.: 32

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: 3 AN: 193062 AF XY: 0.0000193

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: 17 AN: 1391752 Hom.: 0 Cov.: 30 AF XY: 0.0000116 AC XY: 8 AN XY: 688742

African (AFR) AF: 0.00 AC: 0 AN: 30558

American (AMR) AF: 0.000136 AC: 5 AN: 36808

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22834

East Asian (EAS) AF: 0.00 AC: 0 AN: 35736

South Asian (SAS) AF: 0.00 AC: 0 AN: 75550

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51338

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5434

European-Non Finnish (NFE) AF: 0.0000111 AC: 12 AN: 1076232

Other (OTH) AF: 0.00 AC: 0 AN: 57262

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152202 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74344

African (AFR) AF: 0.0000241 AC: 1 AN: 41440

American (AMR) AF: 0.00 AC: 0 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000378

ExAC AF: 0.0000165 AC: 2

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.091	T
BayesDel_noAF	Benign	-0.14
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.23	T
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.024	T
MetaRNN	Uncertain	0.63	D
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		8.8
PrimateAI	Uncertain	0.74	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.23
Sift	Benign	0.049	D
Sift4G	Benign	0.071	T
Polyphen		0.67	P
Vest4		0.89
MutPred		0.68		Gain of methylation at K260 (P = 0.0901)
MVP		0.68
MPC		0.39
ClinPred		0.49	T
GERP RS		6.0
Varity_R		0.65
gMVP		0.89
Mutation Taster		=37/63	disease causing

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

Other links and lift over

dbSNP: rs772143127; hg19: chr11-75508347;