X-70200343-A-G

Position:

• chrX-70200343-A-G

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3 BS2

The NM_198512.3(DGAT2L6):​c.356A>G​(p.Asn119Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000547 in 1,097,724 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes 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: not found (cov: 22)
  • Exomes 𝑓: 0.0000055 (0 hom. 3 hem.)
• Consequence: DGAT2L6 NM_198512.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.14

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]

ACMG classification

Verdict is Likely_benign. Variant got -3 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.764
• BS2: High Hemizygotes in GnomAdExome4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DGAT2L6	NM_198512.3	c.356A>G	p.Asn119Ser	missense_variant	4/7	ENST00000333026.4	NP_940914.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DGAT2L6	ENST00000333026.4	c.356A>G	p.Asn119Ser	missense_variant	4/7	1	NM_198512.3	ENSP00000328036.3

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome AF: 0.00000547 AC: 6 AN: 1097724 Hom.: 0 Cov.: 31 AF XY: 0.00000826 AC XY: 3 AN XY: 363086

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: 0.00000594

Gnomad4 OTH exome AF: 0.0000217

GnomAD4 genome Cov.: 22

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.00000378

EpiCase AF: 0.0000545

EpiControl AF: 0.00

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

Dec 10, 2024

The c.356A>G (p.N119S) alteration is located in exon 4 (coding exon 4) of the DGAT2L6 gene. This alteration results from a A to G substitution at nucleotide position 356, causing the asparagine (N) at amino acid position 119 to be replaced by a serine (S). 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	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.029	D
MetaRNN	Pathogenic	0.76	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	M
PrimateAI	Uncertain	0.50	T
PROVEAN	Uncertain	-4.0	D
REVEL	Benign	0.21
Sift	Uncertain	0.018	D
Sift4G	Benign	0.062	T
Polyphen		0.98	D
Vest4		0.54
MutPred		0.78		Loss of stability (P = 0.2032);
MVP		0.96
MPC		0.16
ClinPred		0.99	D
GERP RS		4.2
Varity_R		0.37
gMVP		0.85

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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

Other links and lift over

dbSNP: rs1427189797; hg19: chrX-69420193;