13-42165425-A-G

Variant summary

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

The NM_178009.5(DGKH):c.950A>G(p.Asp317Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DGKH NM_178009.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.13

Genes affected

DGKH (HGNC:2854): (diacylglycerol kinase eta) This gene encodes a member of the diacylglycerol kinase (DGK) enzyme family. Members of this family are involved in regulating intracellular concentrations of diacylglycerol and phosphatidic acid. Variation in this gene has been associated with bipolar disorder. Alternatively spliced transcript variants have been identified. [provided by RefSeq, Jul 2014]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DGKH	NM_178009.5	c.950A>G	p.Asp317Gly	missense_variant	8/30	ENST00000337343.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DGKH	ENST00000337343.9	c.950A>G	p.Asp317Gly	missense_variant	8/30	1	NM_178009.5	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1402814 Hom.: 0 Cov.: 25 AF XY: 0.00 AC XY: 0 AN XY: 698188

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: 0.00

Gnomad4 OTH exome AF: 0.00

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

Aug 12, 2021

The c.950A>G (p.D317G) alteration is located in exon 8 (coding exon 8) of the DGKH gene. This alteration results from a A to G substitution at nucleotide position 950, causing the aspartic acid (D) at amino acid position 317 to be replaced by a glycine (G). 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	Uncertain	0.49
BayesDel_addAF	Pathogenic	0.37	D
BayesDel_noAF	Pathogenic	0.30
Cadd	Uncertain	25
Dann	Uncertain	0.99
Eigen	Uncertain	0.25
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.98	D;D;.;D;D
M_CAP	Benign	0.056	D
MetaRNN	Uncertain	0.74	D;D;D;D;D
MetaSVM	Uncertain	-0.24	T
MutationAssessor	Benign	1.7	L;L;L;.;.
MutationTaster	Benign	1.0	D;D;D;D;D;D
PrimateAI	Uncertain	0.74	T
REVEL	Uncertain	0.48
Sift4G	Benign	0.29	T;T;T;T;T
Polyphen		0.55	P;B;P;.;B
Vest4		0.92
MutPred		0.44		Gain of loop (P = 0.024);Gain of loop (P = 0.024);Gain of loop (P = 0.024);.;.;
MVP		0.92
MPC		1.2
ClinPred		0.97	D
GERP RS		5.7
Varity_R		0.40
gMVP		0.62

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: chr13-42739561;