chr7-6446081-T-C

Position:

• chr7-6446081-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The ENST00000297056.11(DAGLB):​c.119A>G​(p.Tyr40Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000167 in 1,436,910 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.000017 (0 hom.)
• Consequence: DAGLB ENST00000297056.11 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.38

Genes affected

DAGLB (HGNC:28923): (diacylglycerol lipase beta) Enables lipase activity. Involved in arachidonic acid metabolic process. Located in nucleoplasm and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

KDELR2 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.40536106).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DAGLB	NM_139179.4	c.119A>G	p.Tyr40Cys	missense_variant	2/15	ENST00000297056.11	NP_631918.3
DAGLB	NM_001142936.2	c.119A>G	p.Tyr40Cys	missense_variant	2/13		NP_001136408.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DAGLB	ENST00000297056.11	c.119A>G	p.Tyr40Cys	missense_variant	2/15	1	NM_139179.4	ENSP00000297056.6

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.0000167 AC: 24 AN: 1436910 Hom.: 0 Cov.: 30 AF XY: 0.0000182 AC XY: 13 AN XY: 714506

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: 0.0000208

Gnomad4 OTH exome AF: 0.0000169

GnomAD4 genome Cov.: 30

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

Feb 28, 2024

The c.119A>G (p.Y40C) alteration is located in exon 2 (coding exon 2) of the DAGLB gene. This alteration results from a A to G substitution at nucleotide position 119, causing the tyrosine (Y) at amino acid position 40 to be replaced by a cysteine (C). 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	0.26
BayesDel_addAF	Uncertain	0.078	D
BayesDel_noAF	Benign	-0.13
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.36	T;.;T
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.92	D;D;D
M_CAP	Benign	0.062	D
MetaRNN	Benign	0.41	T;T;T
MetaSVM	Benign	-0.47	T
MutationAssessor	Uncertain	2.5	M;M;.
MutationTaster	Benign	0.61	D;D;D;D;D
PrimateAI	Uncertain	0.61	T
PROVEAN	Uncertain	-3.2	D;N;D
REVEL	Benign	0.28
Sift	Benign	0.047	D;T;T
Sift4G	Uncertain	0.0020	D;D;.
Polyphen		1.0	D;.;.
Vest4		0.84
MutPred		0.33		Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);
MVP		0.73
MPC		0.36
ClinPred		0.98	D
GERP RS		4.6
Varity_R		0.23
gMVP		0.77

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-6485712;