ENST00000499390.2:n.155-157G>A

Variant names:

• chr11-75765150-C-T
• rs10899116
• ENST00000499390.2:n.155-157G>A

Variant summary

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

The ENST00000499390.2(DGAT2-DT):​n.155-157G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 152,216 control chromosomes in the GnomAD database, including 1,047 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 (1047 hom., cov: 32)
• Consequence: DGAT2-DT ENST00000499390.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0990
• Publications: 4 publications found

Genes affected

DGAT2-DT (HGNC:27451): (DGAT2 divergent transcript)

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

ENSG00000300258 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.217 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DGAT2-DT	NR_046090.1	n.155-157G>A		intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DGAT2-DT	ENST00000499390.2	n.155-157G>A		intron_variant	Intron 1 of 3	1
DGAT2	ENST00000603276.5	c.-153+5524C>T		intron_variant	Intron 1 of 5	5		ENSP00000474015.1
ENSG00000300258	ENST00000770408.1	n.181+4599G>A		intron_variant	Intron 1 of 2
DGAT2-DT	ENST00000770757.1	n.181+3344G>A		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17361 AN: 152098 Hom.: 1049 Cov.: 32

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.219

Gnomad AMR AF: 0.104

Gnomad ASJ AF: 0.0894

Gnomad EAS AF: 0.227

Gnomad SAS AF: 0.0926

Gnomad FIN AF: 0.0985

Gnomad MID AF: 0.0860

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.101

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

GnomAD4 genome AF: 0.114 AC: 17371 AN: 152216 Hom.: 1047 Cov.: 32 AF XY: 0.113 AC XY: 8389 AN XY: 74424

African (AFR) AF: 0.130 AC: 5410 AN: 41528

American (AMR) AF: 0.104 AC: 1595 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0894 AC: 310 AN: 3468

East Asian (EAS) AF: 0.228 AC: 1180 AN: 5176

South Asian (SAS) AF: 0.0921 AC: 444 AN: 4822

European-Finnish (FIN) AF: 0.0985 AC: 1046 AN: 10620

Middle Eastern (MID) AF: 0.0788 AC: 23 AN: 292

European-Non Finnish (NFE) AF: 0.102 AC: 6949 AN: 67996

Other (OTH) AF: 0.102 AC: 215 AN: 2110

Alfa AF: 0.102 Hom.: 1065

Bravo AF: 0.116

Asia WGS AF: 0.177 AC: 615 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.6
DANN	Benign	0.39
PhyloP100		-0.099

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10899116; hg19: chr11-75476195;