11-75772578-A-G

Variant names:

• chr11-75772578-A-G
• rs1944438
• NM_032564.5:c.121+3466A>G

Variant summary

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

The NM_032564.5(DGAT2):​c.121+3466A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.399 in 152,030 control chromosomes in the GnomAD database, including 14,622 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 0.40 (14622 hom., cov: 32)
• Consequence: DGAT2 NM_032564.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.129
• Publications: 6 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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.542 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.121+3466A>G		intron	N/A	NP_115953.2
	DGAT2	NM_001253891.2		c.121+3466A>G		intron	N/A	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.121+3466A>G		intron	N/A	ENSP00000228027.6	Q96PD7-1
	DGAT2	ENST00000376262.7	TSL:1	c.121+3466A>G		intron	N/A	ENSP00000365438.3	Q96PD7-2
	DGAT2	ENST00000604733.5	TSL:1	c.112+3466A>G		intron	N/A	ENSP00000474668.1	S4R3S3

Frequencies

GnomAD3 genomes AF: 0.400 AC: 60701 AN: 151912 Hom.: 14621 Cov.: 32

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.533

Gnomad AMR AF: 0.418

Gnomad ASJ AF: 0.468

Gnomad EAS AF: 0.173

Gnomad SAS AF: 0.388

Gnomad FIN AF: 0.518

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.547

Gnomad OTH AF: 0.464

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

GnomAD4 genome AF: 0.399 AC: 60713 AN: 152030 Hom.: 14622 Cov.: 32 AF XY: 0.398 AC XY: 29562 AN XY: 74308

African (AFR) AF: 0.137 AC: 5672 AN: 41452

American (AMR) AF: 0.417 AC: 6366 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.468 AC: 1624 AN: 3470

East Asian (EAS) AF: 0.173 AC: 895 AN: 5168

South Asian (SAS) AF: 0.389 AC: 1877 AN: 4822

European-Finnish (FIN) AF: 0.518 AC: 5484 AN: 10578

Middle Eastern (MID) AF: 0.561 AC: 165 AN: 294

European-Non Finnish (NFE) AF: 0.547 AC: 37159 AN: 67954

Other (OTH) AF: 0.467 AC: 985 AN: 2110

Alfa AF: 0.501 Hom.: 8930

Bravo AF: 0.382

Asia WGS AF: 0.285 AC: 992 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.3
DANN	Benign	0.22
PhyloP100		-0.13
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: rs1944438; hg19: chr11-75483623;