Variant 11-75796495-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_032564.5(DGAT2):c.597C>A(p.Phe199Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,210 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

DGAT2
NM_032564.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.820

Variant links:

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 links:

DGAT2 (HGNC:):

DGAT2 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.969

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DGAT2	NM_032564.5 linkuse as main transcript	c.597C>A	p.Phe199Leu	missense_variant	5/8	ENST00000228027.12	NP_115953.2	Q96PD7-1
DGAT2	NM_001253891.2 linkuse as main transcript	c.468C>A	p.Phe156Leu	missense_variant	4/7		NP_001240820.1	Q96PD7-2
DGAT2	XM_011545304.3 linkuse as main transcript	c.507C>A	p.Phe169Leu	missense_variant	5/8		XP_011543606.1
DGAT2	XM_047427716.1 linkuse as main transcript	c.324C>A	p.Phe108Leu	missense_variant	5/8		XP_047283672.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DGAT2	ENST00000228027.12 linkuse as main transcript	c.597C>A	p.Phe199Leu	missense_variant	5/8	1	NM_032564.5	ENSP00000228027.6		Q96PD7-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152210

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 26, 2024

The c.597C>A (p.F199L) alteration is located in exon 5 (coding exon 5) of the DGAT2 gene. This alteration results from a C to A substitution at nucleotide position 597, causing the phenylalanine (F) at amino acid position 199 to be replaced by a leucine (L). 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

Pathogenic

0.99

BayesDel_addAF

Pathogenic

0.21

BayesDel_noAF

Uncertain

0.070

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.27

.;.;T;.;.;.

Eigen

Uncertain

0.35

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.85

D;D;D;D;D;T

M_CAP

Benign

0.048

MetaRNN

Pathogenic

0.97

D;D;D;D;D;D

MetaSVM

Benign

-0.92

MutationAssessor

Uncertain

2.7

.;.;M;.;.;.

PrimateAI

Pathogenic

0.84

PROVEAN

Pathogenic

-5.5

.;.;D;D;.;.

REVEL

Uncertain

0.39

Sift

Uncertain

0.021

.;.;D;D;.;.

Sift4G

Uncertain

0.057

T;D;D;T;T;D

Polyphen

1.0, 0.84

.;.;D;P;.;.

Vest4

0.98, 0.97

MutPred

0.97

.;.;Gain of helix (P = 0.2059);.;.;.;

MVP

0.43

MPC

0.61

ClinPred

0.96

GERP RS

2.8

Varity_R

0.72

gMVP

0.94

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over