12-55939439-A-C

Position:

• chr12-55939439-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001351038.2(DGKA):​c.-355A>C variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: DGKA NM_001351038.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.991

Genes affected

DGKA (HGNC:2849): (diacylglycerol kinase alpha) The protein encoded by this gene belongs to the eukaryotic diacylglycerol kinase family. It acts as a modulator that competes with protein kinase C for the second messenger diacylglycerol in intracellular signaling pathways. It also plays an important role in the resynthesis of phosphatidylinositols and phosphorylating diacylglycerol to phosphatidic acid. Several transcript variants encoding different isoforms have been identified for this gene. [provided by RefSeq, Apr 2017]

DGKA (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1147553).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DGKA	NM_001345.5	c.619A>C	p.Met207Leu	missense_variant	9/24	ENST00000331886.10	NP_001336.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DGKA	ENST00000331886.10	c.619A>C	p.Met207Leu	missense_variant	9/24	5	NM_001345.5	ENSP00000328405.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

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

May 27, 2022

The c.619A>C (p.M207L) alteration is located in exon 9 (coding exon 8) of the DGKA gene. This alteration results from a A to C substitution at nucleotide position 619, causing the methionine (M) at amino acid position 207 to be replaced by a leucine (L). 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	0.077
BayesDel_addAF	Benign	-0.028	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	14
DANN	Benign	0.50
DEOGEN2	Benign	0.24	T;.;T;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.91
FATHMM_MKL	Benign	0.64	D
LIST_S2	Benign	0.77	.;T;T;.
M_CAP	Benign	0.052	D
MetaRNN	Benign	0.11	T;T;T;T
MetaSVM	Benign	-0.65	T
MutationAssessor	Benign	0.020	N;.;N;N
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	0.28	N;N;N;N
REVEL	Benign	0.25
Sift	Benign	1.0	T;T;T;T
Sift4G	Benign	0.99	T;T;T;T
Polyphen		0.0	B;B;B;B
Vest4		0.18
MutPred		0.56		Gain of catalytic residue at K211 (P = 0);.;Gain of catalytic residue at K211 (P = 0);Gain of catalytic residue at K211 (P = 0);
MVP		0.26
MPC		0.52
ClinPred		0.031	T
GERP RS		2.7
Varity_R		0.036
gMVP		0.51

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: chr12-56333223;