Variant X-70204388-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_198512.3(DGAT2L6):c.731T>G(p.Leu244Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000777 in 1,209,521 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 17 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L244S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00040 ( 0 hom., 8 hem., cov: 22)

Exomes 𝑓: 0.000045 ( 0 hom. 9 hem. )

Consequence

DGAT2L6
NM_198512.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.531

Variant links:

Genes affected

DGAT2L6 (HGNC:23250): (diacylglycerol O-acyltransferase 2 like 6) This gene is a member of the diacylglycerol acyltransferase 2 family. The encoded protein is a putative acyltransferase and is most likely involved in the synthesis of di- or triacylglycerol, however its substrate specificity is currently unknown. [provided by RefSeq, Feb 2015]

DGAT2L6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.023869365).

BS2

High Hemizygotes in GnomAd at 8 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DGAT2L6	NM_198512.3 linkuse as main transcript	c.731T>G	p.Leu244Trp	missense_variant	6/7	ENST00000333026.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DGAT2L6	ENST00000333026.4 linkuse as main transcript	c.731T>G	p.Leu244Trp	missense_variant	6/7	1	NM_198512.3	P1

Frequencies

GnomAD3 genomes

AF:

0.000404

AC:

AN:

111475

Hom.:

Cov.:

AF XY:

0.000238

AC XY:

AN XY:

33659

show subpopulations

Gnomad AFR

AF:

0.00137

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000190

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:

0.000668

GnomAD3 exomes

AF:

0.000110

AC:

AN:

182448

Hom.:

AF XY:

0.0000298

AC XY:

AN XY:

67026

show subpopulations

Gnomad AFR exome

AF:

0.00122

Gnomad AMR exome

AF:

0.000110

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000222

GnomAD4 exome

AF:

0.0000446

AC:

AN:

1097992

Hom.:

Cov.:

AF XY:

0.0000248

AC XY:

AN XY:

363372

show subpopulations

Gnomad4 AFR exome

AF:

0.00140

Gnomad4 AMR exome

AF:

0.0000853

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:

0.00000356

Gnomad4 OTH exome

AF:

0.000130

GnomAD4 genome

AF:

0.000403

AC:

AN:

111529

Hom.:

Cov.:

AF XY:

0.000237

AC XY:

AN XY:

33723

show subpopulations

Gnomad4 AFR

AF:

0.00137

Gnomad4 AMR

AF:

0.000190

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:

0.000660

Alfa

AF:

0.0000637

Hom.:

Bravo

AF:

0.000480

ESP6500AA

AF:

0.000782

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000906

AC:

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 30, 2022

The c.731T>G (p.L244W) alteration is located in exon 6 (coding exon 6) of the DGAT2L6 gene. This alteration results from a T to G substitution at nucleotide position 731, causing the leucine (L) at amino acid position 244 to be replaced by a tryptophan (W). 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

0.078

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.81

Cadd

Benign

Dann

Benign

0.71

DEOGEN2

Benign

0.022

FATHMM_MKL

Benign

0.057

LIST_S2

Benign

0.21

M_CAP

Benign

0.010

MetaRNN

Benign

0.024

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

MutationTaster

Benign

1.0

PrimateAI

Benign

0.34

PROVEAN

Benign

0.74

REVEL

Benign

0.073

Sift

Benign

0.65

Sift4G

Benign

0.21

Polyphen

0.73

Vest4

0.36

MVP

0.58

MPC

0.10

ClinPred

0.024

GERP RS

1.9

Varity_R

0.025

gMVP

0.55

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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