11-75800498-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032564.5(DGAT2):c.1157A>C(p.Glu386Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: DGAT2 NM_032564.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.55

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24343851).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DGAT2	NM_032564.5	c.1157A>C	p.Glu386Ala	missense_variant	8/8	ENST00000228027.12
DGAT2	NM_001253891.2	c.1028A>C	p.Glu343Ala	missense_variant	7/7
DGAT2	XM_011545304.3	c.1067A>C	p.Glu356Ala	missense_variant	8/8
DGAT2	XM_047427716.1	c.884A>C	p.Glu295Ala	missense_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DGAT2	ENST00000228027.12	c.1157A>C	p.Glu386Ala	missense_variant	8/8	1	NM_032564.5	P1
DGAT2	ENST00000376262.7	c.1028A>C	p.Glu343Ala	missense_variant	7/7	1
DGAT2	ENST00000603363.5	n.4897A>C		non_coding_transcript_exon_variant	4/4	2
DGAT2	ENST00000603865.1	n.2544A>C		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 23, 2023

The c.1157A>C (p.E386A) alteration is located in exon 8 (coding exon 8) of the DGAT2 gene. This alteration results from a A to C substitution at nucleotide position 1157, causing the glutamic acid (E) at amino acid position 386 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
Cadd	Benign	22
Dann	Uncertain	0.99
DEOGEN2	Benign	0.076	T;.
Eigen	Benign	0.13
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.92	D;D
M_CAP	Benign	0.0072	T
MetaRNN	Benign	0.24	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.38	N;N
REVEL	Benign	0.059
Sift	Benign	0.14	T;T
Sift4G	Benign	0.21	T;T
Polyphen		0.42	B;B
Vest4		0.21
MutPred		0.39		Loss of disorder (P = 0.0644);.;
MVP		0.51
MPC		0.25
ClinPred		0.60	D
GERP RS		5.5
Varity_R		0.10
gMVP		0.63

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-75511543;