chr11-75797272-G-A

Variant names:

• chr11-75797272-G-A
• rs151179593
• NM_032564.5:c.749G>A

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Moderate BP6 BS2

The NM_032564.5(DGAT2):​c.749G>A​(p.Gly250Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00137 in 1,574,470 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.0011 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0014 (2 hom.)
• Consequence: DGAT2 NM_032564.5 missense
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:1
• Conservation: PhyloP100: 9.49
• Publications: 5 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: Benign. The variant received -7 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.068149924).
• BP6: Variant 11-75797272-G-A is Benign according to our data. Variant chr11-75797272-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 2642161.
• BS2: High AC in GnomAd4 at 173 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.749G>A	p.Gly250Asp	missense	Exon 6 of 8	NP_115953.2
	DGAT2	NM_001253891.2		c.620G>A	p.Gly207Asp	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.749G>A	p.Gly250Asp	missense	Exon 6 of 8	ENSP00000228027.6	Q96PD7-1
	DGAT2	ENST00000376262.7	TSL:1	c.620G>A	p.Gly207Asp	missense	Exon 5 of 7	ENSP00000365438.3	Q96PD7-2
	DGAT2	ENST00000604733.5	TSL:1	c.611G>A	p.Gly204Asp	missense	Exon 5 of 7	ENSP00000474668.1	S4R3S3

Frequencies

GnomAD3 genomes AF: 0.00114 AC: 173 AN: 152178 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000362

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00249

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.000471

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00166

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.00115 AC: 250 AN: 216904 AF XY: 0.00111

Gnomad AFR exome AF: 0.000279

Gnomad AMR exome AF: 0.00121

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00135

Gnomad NFE exome AF: 0.00173

Gnomad OTH exome AF: 0.000399

GnomAD4 exome AF: 0.00140 AC: 1985 AN: 1422174 Hom.: 2 Cov.: 30 AF XY: 0.00140 AC XY: 987 AN XY: 706590

African (AFR) AF: 0.000128 AC: 4 AN: 31370

American (AMR) AF: 0.00142 AC: 56 AN: 39396

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24700

East Asian (EAS) AF: 0.00 AC: 0 AN: 36720

South Asian (SAS) AF: 0.000544 AC: 44 AN: 80874

European-Finnish (FIN) AF: 0.000684 AC: 36 AN: 52654

Middle Eastern (MID) AF: 0.00161 AC: 9 AN: 5598

European-Non Finnish (NFE) AF: 0.00161 AC: 1764 AN: 1092278

Other (OTH) AF: 0.00123 AC: 72 AN: 58584

GnomAD4 genome AF: 0.00114 AC: 173 AN: 152296 Hom.: 1 Cov.: 32 AF XY: 0.00102 AC XY: 76 AN XY: 74464

African (AFR) AF: 0.000361 AC: 15 AN: 41568

American (AMR) AF: 0.00248 AC: 38 AN: 15298

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.000471 AC: 5 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00166 AC: 113 AN: 68014

Other (OTH) AF: 0.000473 AC: 1 AN: 2114

Alfa AF: 0.00157 Hom.: 4

Bravo AF: 0.00139

TwinsUK AF: 0.00108 AC: 4

ALSPAC AF: 0.00285 AC: 11

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.00186 AC: 16

ExAC AF: 0.00121 AC: 147

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.43
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Uncertain	0.020
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.24	T
Eigen	Pathogenic	0.93
Eigen_PC	Pathogenic	0.93
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.86	D
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.068	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		9.5
PrimateAI	Uncertain	0.71	T
PROVEAN	Pathogenic	-5.6	D
REVEL	Uncertain	0.53
Sift	Uncertain	0.010	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.91
MVP		0.79
MPC		0.64
ClinPred		0.080	T
GERP RS		6.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.91
gMVP		0.88
Mutation Taster		=23/77	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: rs151179593; hg19: chr11-75508317;