X-70177608-T-C

Variant summary

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

The NM_198512.3(DGAT2L6):ā€‹c.26T>Cā€‹(p.Leu9Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000331 in 1,209,405 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. 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: š‘“ 0.0000089 ( 0 hom., 0 hem., cov: 23)
Exomes š‘“: 0.0000027 ( 0 hom. 0 hem. )

Consequence

DGAT2L6
NM_198512.3 missense

Scores

1
5
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.17
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]

Genome browser will be placed here

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, 0.963

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
DGAT2L6NM_198512.3 linkuse as main transcriptc.26T>C p.Leu9Pro missense_variant 1/7 ENST00000333026.4 NP_940914.1 Q6ZPD8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
DGAT2L6ENST00000333026.4 linkuse as main transcriptc.26T>C p.Leu9Pro missense_variant 1/71 NM_198512.3 ENSP00000328036.3 Q6ZPD8

Frequencies

GnomAD3 genomes
AF:
0.00000892
AC:
1
AN:
112073
Hom.:
0
Cov.:
23
AF XY:
0.00
AC XY:
0
AN XY:
34281
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.0000188
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000273
AC:
3
AN:
1097332
Hom.:
0
Cov.:
29
AF XY:
0.00
AC XY:
0
AN XY:
362724
show subpopulations
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:
0.00000238
Gnomad4 OTH exome
AF:
0.0000217
GnomAD4 genome
AF:
0.00000892
AC:
1
AN:
112073
Hom.:
0
Cov.:
23
AF XY:
0.00
AC XY:
0
AN XY:
34281
show subpopulations
Gnomad4 AFR
AF:
0.00
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:
0.0000188
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 submitterclinical testingAmbry GeneticsSep 01, 2024The c.26T>C (p.L9P) alteration is located in exon 1 (coding exon 1) of the DGAT2L6 gene. This alteration results from a T to C substitution at nucleotide position 26, causing the leucine (L) at amino acid position 9 to be replaced by a proline (P). 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
0.13
BayesDel_addAF
Benign
-0.17
T
BayesDel_noAF
Benign
-0.49
CADD
Benign
21
DANN
Uncertain
1.0
DEOGEN2
Benign
0.21
T
FATHMM_MKL
Benign
0.56
D
LIST_S2
Benign
0.41
T
M_CAP
Benign
0.016
T
MetaRNN
Pathogenic
0.96
D
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.0
N
PrimateAI
Benign
0.43
T
PROVEAN
Uncertain
-2.9
D
REVEL
Uncertain
0.31
Sift
Uncertain
0.0020
D
Sift4G
Uncertain
0.0030
D
Polyphen
1.0
D
Vest4
0.57
MutPred
0.87
Gain of disorder (P = 0.013);
MVP
0.48
MPC
0.13
ClinPred
0.79
D
GERP RS
4.7
Varity_R
0.79
gMVP
0.84

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.

Other links and lift over

dbSNP: rs2085330907; hg19: chrX-69397458; API