11-75800527-T-C

Variant names:

• chr11-75800527-T-C
• rs3060
• NM_032564.5:c.*19T>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.*19T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 1,611,350 control chromosomes in the GnomAD database, including 17,817 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 0.21 (5491 hom., cov: 33)
  • Exomes 𝑓: 0.11 (12326 hom.)
• Consequence: DGAT2 NM_032564.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.677
• Publications: 24 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.464 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DGAT2	NM_032564.5	MANE Select	c.*19T>C		3_prime_UTR	Exon 8 of 8	NP_115953.2
	DGAT2	NM_001253891.2		c.*19T>C		3_prime_UTR	Exon 7 of 7	NP_001240820.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DGAT2	ENST00000228027.12	TSL:1 MANE Select	c.*19T>C		3_prime_UTR	Exon 8 of 8	ENSP00000228027.6
	DGAT2	ENST00000376262.7	TSL:1	c.*19T>C		3_prime_UTR	Exon 7 of 7	ENSP00000365438.3
	DGAT2	ENST00000603363.5	TSL:2	n.4926T>C		non_coding_transcript_exon	Exon 4 of 4

Frequencies

GnomAD3 genomes AF: 0.211 AC: 32110 AN: 152102 Hom.: 5471 Cov.: 33

Gnomad AFR AF: 0.469

Gnomad AMI AF: 0.219

Gnomad AMR AF: 0.142

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.265

Gnomad SAS AF: 0.130

Gnomad FIN AF: 0.0778

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0984

Gnomad OTH AF: 0.176

GnomAD2 exomes AF: 0.140 AC: 34340 AN: 245940 AF XY: 0.132

Gnomad AFR exome AF: 0.479

Gnomad AMR exome AF: 0.116

Gnomad ASJ exome AF: 0.117

Gnomad EAS exome AF: 0.268

Gnomad FIN exome AF: 0.0874

Gnomad NFE exome AF: 0.0946

Gnomad OTH exome AF: 0.126

GnomAD4 exome AF: 0.109 AC: 159181 AN: 1459130 Hom.: 12326 Cov.: 31 AF XY: 0.108 AC XY: 78594 AN XY: 725666

African (AFR) AF: 0.481 AC: 16077 AN: 33408

American (AMR) AF: 0.116 AC: 5145 AN: 44292

Ashkenazi Jewish (ASJ) AF: 0.116 AC: 3010 AN: 26036

East Asian (EAS) AF: 0.292 AC: 11576 AN: 39614

South Asian (SAS) AF: 0.125 AC: 10699 AN: 85814

European-Finnish (FIN) AF: 0.0875 AC: 4659 AN: 53256

Middle Eastern (MID) AF: 0.116 AC: 669 AN: 5754

European-Non Finnish (NFE) AF: 0.0894 AC: 99309 AN: 1110674

Other (OTH) AF: 0.133 AC: 8037 AN: 60282

GnomAD4 genome AF: 0.211 AC: 32180 AN: 152220 Hom.: 5491 Cov.: 33 AF XY: 0.207 AC XY: 15426 AN XY: 74424

African (AFR) AF: 0.470 AC: 19488 AN: 41504

American (AMR) AF: 0.142 AC: 2167 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.117 AC: 405 AN: 3470

East Asian (EAS) AF: 0.266 AC: 1378 AN: 5178

South Asian (SAS) AF: 0.129 AC: 622 AN: 4822

European-Finnish (FIN) AF: 0.0778 AC: 825 AN: 10606

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.0984 AC: 6692 AN: 68018

Other (OTH) AF: 0.177 AC: 375 AN: 2114

Alfa AF: 0.133 Hom.: 6811

Bravo AF: 0.226

Asia WGS AF: 0.252 AC: 876 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.92
DANN	Benign	0.44
PhyloP100		-0.68
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: rs3060; hg19: chr11-75511572; COSMIC: COSV57176294; COSMIC: COSV57176294;