4-961844-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001347.4(DGKQ):c.2316-10C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00274 in 1,592,816 control chromosomes in the GnomAD database, including 94 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.013 (47 hom., cov: 33)
  • Exomes 𝑓: 0.0016 (47 hom.)
• Consequence: DGKQ NM_001347.4 splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00001241
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.98

Genes affected

DGKQ (HGNC:2856): (diacylglycerol kinase theta) The protein encoded by this gene contains three cysteine-rich domains, a proline-rich region, and a pleckstrin homology domain with an overlapping Ras-associating domain. It is localized in the speckle domains of the nucleus, and mediates the regeneration of phosphatidylinositol (PI) from diacylglycerol in the PI-cycle during cell signal transduction. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 4-961844-G-A is Benign according to our data. Variant chr4-961844-G-A is described in ClinVar as [Benign]. Clinvar id is 791615.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0135 (2050/152254) while in subpopulation AFR AF= 0.0454 (1884/41530). AF 95% confidence interval is 0.0437. There are 47 homozygotes in gnomad4. There are 963 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 45 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DGKQ	NM_001347.4	c.2316-10C>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000273814.8
DGKQ	XM_011513411.2	c.2316-10C>T		splice_polypyrimidine_tract_variant, intron_variant
DGKQ	XM_047449687.1	c.2403-10C>T		splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DGKQ	ENST00000273814.8	c.2316-10C>T		splice_polypyrimidine_tract_variant, intron_variant		1	NM_001347.4	P1
DGKQ	ENST00000509465.5	c.2117-10C>T		splice_polypyrimidine_tract_variant, intron_variant		5
DGKQ	ENST00000515182.1	c.107+138C>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.0134 AC: 2042 AN: 152136 Hom.: 45 Cov.: 33

Gnomad AFR AF: 0.0453

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00660

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000620

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000618

Gnomad OTH AF: 0.00907

GnomAD3 exomes AF: 0.00395 AC: 925 AN: 234038 Hom.: 16 AF XY: 0.00302 AC XY: 381 AN XY: 125968

Gnomad AFR exome AF: 0.0455

Gnomad AMR exome AF: 0.00387

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000743

Gnomad FIN exome AF: 0.0000512

Gnomad NFE exome AF: 0.000255

Gnomad OTH exome AF: 0.00283

GnomAD4 exome AF: 0.00160 AC: 2308 AN: 1440562 Hom.: 47 Cov.: 34 AF XY: 0.00142 AC XY: 1014 AN XY: 714450

Gnomad4 AFR exome AF: 0.0456

Gnomad4 AMR exome AF: 0.00413

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000973

Gnomad4 FIN exome AF: 0.0000994

Gnomad4 NFE exome AF: 0.000246

Gnomad4 OTH exome AF: 0.00393

GnomAD4 genome AF: 0.0135 AC: 2050 AN: 152254 Hom.: 47 Cov.: 33 AF XY: 0.0129 AC XY: 963 AN XY: 74454

Gnomad4 AFR AF: 0.0454

Gnomad4 AMR AF: 0.00653

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.0000942

Gnomad4 NFE AF: 0.000618

Gnomad4 OTH AF: 0.00898

Alfa AF: 0.00943 Hom.: 11

Bravo AF: 0.0151

Asia WGS AF: 0.00318 AC: 11 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Aug 15, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	0.025
Dann	Benign	0.53
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000012
dbscSNV1_RF	Benign	0.0
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

Other links and lift over

dbSNP: rs77865682; hg19: chr4-955632;