rs1017713

Variant names:

• chr11-75788407-T-C
• rs1017713
• NM_032564.5:c.251-1781T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032564.5(DGAT2):​c.251-1781T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 152,270 control chromosomes in the GnomAD database, including 965 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.11 (965 hom., cov: 32)
• Consequence: DGAT2 NM_032564.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.170
• Publications: 8 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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

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.251-1781T>C		intron	N/A	NP_115953.2
	DGAT2	NM_001253891.2		c.122-1781T>C		intron	N/A	NP_001240820.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DGAT2	ENST00000228027.12	TSL:1 MANE Select	c.251-1781T>C		intron	N/A	ENSP00000228027.6
	DGAT2	ENST00000376262.7	TSL:1	c.122-1781T>C		intron	N/A	ENSP00000365438.3
	DGAT2	ENST00000604733.5	TSL:1	c.113-1781T>C		intron	N/A	ENSP00000474668.1

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16492 AN: 152152 Hom.: 967 Cov.: 32

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.219

Gnomad AMR AF: 0.104

Gnomad ASJ AF: 0.0962

Gnomad EAS AF: 0.224

Gnomad SAS AF: 0.0938

Gnomad FIN AF: 0.0730

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0961

Gnomad OTH AF: 0.0995

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.108 AC: 16500 AN: 152270 Hom.: 965 Cov.: 32 AF XY: 0.106 AC XY: 7928 AN XY: 74458

African (AFR) AF: 0.126 AC: 5219 AN: 41552

American (AMR) AF: 0.104 AC: 1585 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0962 AC: 334 AN: 3472

East Asian (EAS) AF: 0.225 AC: 1167 AN: 5182

South Asian (SAS) AF: 0.0933 AC: 450 AN: 4824

European-Finnish (FIN) AF: 0.0730 AC: 775 AN: 10612

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0961 AC: 6537 AN: 68010

Other (OTH) AF: 0.101 AC: 213 AN: 2112

Alfa AF: 0.0973 Hom.: 1020

Bravo AF: 0.111

Asia WGS AF: 0.170 AC: 589 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	8.3
DANN	Benign	0.64
PhyloP100		-0.17
Mutation Taster		=100/0	polymorphism (auto)

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: rs1017713; hg19: chr11-75499452;