Variant X-70200270-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_198512.3(DGAT2L6):c.283G>A(p.Asp95Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000062 in 1,209,292 control chromosomes in the GnomAD database, including 1 homozygotes. There are 23 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00029 ( 1 hom., 7 hem., cov: 22)

Exomes 𝑓: 0.000039 ( 0 hom. 16 hem. )

Consequence

DGAT2L6
NM_198512.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.24

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High Hemizygotes in GnomAd at 7 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DGAT2L6	NM_198512.3 linkuse as main transcript	c.283G>A	p.Asp95Asn	missense_variant	4/7	ENST00000333026.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DGAT2L6	ENST00000333026.4 linkuse as main transcript	c.283G>A	p.Asp95Asn	missense_variant	4/7	1	NM_198512.3	P1

Frequencies

GnomAD3 genomes

AF:

0.000287

AC:

AN:

111480

Hom.:

Cov.:

AF XY:

0.000208

AC XY:

AN XY:

33666

show subpopulations

Gnomad AFR

AF:

0.0000327

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00266

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:

0.00200

GnomAD3 exomes

AF:

0.0000382

AC:

AN:

183225

Hom.:

AF XY:

0.0000443

AC XY:

AN XY:

67751

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000729

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:

0.00111

GnomAD4 exome

AF:

0.0000392

AC:

AN:

1097760

Hom.:

Cov.:

AF XY:

0.0000441

AC XY:

AN XY:

363122

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000738

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:

0.00000119

Gnomad4 OTH exome

AF:

0.000347

GnomAD4 genome

AF:

0.000287

AC:

AN:

111532

Hom.:

Cov.:

AF XY:

0.000208

AC XY:

AN XY:

33728

show subpopulations

Gnomad4 AFR

AF:

0.0000326

Gnomad4 AMR

AF:

0.00265

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:

0.00197

Alfa

AF:

0.0000868

Hom.:

Bravo

AF:

0.000642

ExAC

AF:

0.0000412

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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

Aug 20, 2023

The c.283G>A (p.D95N) alteration is located in exon 4 (coding exon 4) of the DGAT2L6 gene. This alteration results from a G to A substitution at nucleotide position 283, causing the aspartic acid (D) at amino acid position 95 to be replaced by an asparagine (N). 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

0.10

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.99

Cadd

Benign

Dann

Uncertain

0.99

DEOGEN2

Benign

0.15

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.80

M_CAP

Benign

0.0072

MetaRNN

Benign

0.064

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.1

MutationTaster

Benign

0.99

PrimateAI

Benign

0.39

PROVEAN

Uncertain

-2.5

REVEL

Benign

0.13

Sift

Benign

0.36

Sift4G

Benign

0.29

Polyphen

0.48

Vest4

0.12

MutPred

0.50

Gain of MoRF binding (P = 0.0631);

MVP

0.15

MPC

0.030

ClinPred

0.16

GERP RS

5.2

Varity_R

0.19

gMVP

0.65

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.21

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.21

Position offset: -15

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