rs3060

Positions:

• chr11-75800527-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 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. Variant has been reported in Lovd as Benign (no stars).

• 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

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]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 11-75800527-T-C is Benign according to our data. Variant chr11-75800527-T-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.464 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DGAT2	NM_032564.5	c.*19T>C		3_prime_UTR_variant	8/8	ENST00000228027.12	NP_115953.2
DGAT2	NM_001253891.2	c.*19T>C		3_prime_UTR_variant	7/7		NP_001240820.1
DGAT2	XM_011545304.3	c.*19T>C		3_prime_UTR_variant	8/8		XP_011543606.1
DGAT2	XM_047427716.1	c.*19T>C		3_prime_UTR_variant	8/8		XP_047283672.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DGAT2	ENST00000228027.12	c.*19T>C		3_prime_UTR_variant	8/8	1	NM_032564.5	ENSP00000228027	P1
DGAT2	ENST00000376262.7	c.*19T>C		3_prime_UTR_variant	7/7	1		ENSP00000365438
DGAT2	ENST00000603363.5	n.4926T>C		non_coding_transcript_exon_variant	4/4	2
DGAT2	ENST00000603865.1	n.2573T>C		non_coding_transcript_exon_variant	3/3	2

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

GnomAD3 exomes AF: 0.140 AC: 34340 AN: 245940 Hom.: 3677 AF XY: 0.132 AC XY: 17604 AN XY: 132956

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 SAS exome AF: 0.124

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

Gnomad4 AFR exome AF: 0.481

Gnomad4 AMR exome AF: 0.116

Gnomad4 ASJ exome AF: 0.116

Gnomad4 EAS exome AF: 0.292

Gnomad4 SAS exome AF: 0.125

Gnomad4 FIN exome AF: 0.0875

Gnomad4 NFE exome AF: 0.0894

Gnomad4 OTH exome AF: 0.133

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

Gnomad4 AFR AF: 0.470

Gnomad4 AMR AF: 0.142

Gnomad4 ASJ AF: 0.117

Gnomad4 EAS AF: 0.266

Gnomad4 SAS AF: 0.129

Gnomad4 FIN AF: 0.0778

Gnomad4 NFE AF: 0.0984

Gnomad4 OTH AF: 0.177

Alfa AF: 0.110 Hom.: 2550

Bravo AF: 0.226

Asia WGS AF: 0.252 AC: 876 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.92
DANN	Benign	0.44

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

Publications

LitVar

Other links and lift over

dbSNP: rs3060; hg19: chr11-75511572; COSMIC: COSV57176294; COSMIC: COSV57176294;