11-75797190-T-C

Position:

• chr11-75797190-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_032564.5(DGAT2):​c.667T>C​(p.Tyr223His) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DGAT2 NM_032564.5 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 5.87

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DGAT2	NM_032564.5	c.667T>C	p.Tyr223His	missense_variant	6/8	ENST00000228027.12	NP_115953.2
DGAT2	NM_001253891.2	c.538T>C	p.Tyr180His	missense_variant	5/7		NP_001240820.1
DGAT2	XM_011545304.3	c.577T>C	p.Tyr193His	missense_variant	6/8		XP_011543606.1
DGAT2	XM_047427716.1	c.394T>C	p.Tyr132His	missense_variant	6/8		XP_047283672.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DGAT2	ENST00000228027.12	c.667T>C	p.Tyr223His	missense_variant	6/8	1	NM_032564.5	ENSP00000228027.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1396898 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 691264

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, no assertion criteria provided

literature only

OMIM

Apr 21, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Uncertain	0.086	D
BayesDel_noAF	Benign	-0.11
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.14	.;T;.;.
Eigen	Benign	0.016
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.91	D;D;D;D
M_CAP	Benign	0.011	T
MetaRNN	Uncertain	0.51	D;D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	.;L;.;.
PrimateAI	Pathogenic	0.80	T
PROVEAN	Uncertain	-2.6	.;D;D;.
REVEL	Benign	0.20
Sift	Benign	0.43	.;T;T;.
Sift4G	Benign	0.49	T;T;T;T
Polyphen		0.026, 0.020	.;B;B;.
Vest4		0.55, 0.55
MutPred		0.65		.;Gain of disorder (P = 0.0281);.;.;
MVP		0.41
MPC		0.24
ClinPred		0.80	D
GERP RS		6.0
Varity_R		0.41
gMVP		0.80

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: rs869025595; hg19: chr11-75508235;