Variant 4-961844-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

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, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.98

Variant links:

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]

DGKQ links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 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_multiple_submitters_no_conflicts, 2 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 GnomAd4 at 47 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
DGKQ	NM_001347.4 linkuse as main transcript	c.2316-10C>T	splice_polypyrimidine_tract_variant, intron_variant	ENST00000273814.8	NP_001338.2
DGKQ	XM_011513411.2 linkuse as main transcript	c.2316-10C>T	splice_polypyrimidine_tract_variant, intron_variant		XP_011511713.1
DGKQ	XM_047449687.1 linkuse as main transcript	c.2403-10C>T	splice_polypyrimidine_tract_variant, intron_variant		XP_047305643.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris
DGKQ	ENST00000273814.8 linkuse as main transcript	c.2316-10C>T	splice_polypyrimidine_tract_variant, intron_variant	1	NM_001347.4	ENSP00000273814	P1
DGKQ	ENST00000509465.5 linkuse as main transcript	c.2117-10C>T	splice_polypyrimidine_tract_variant, intron_variant	5		ENSP00000425862
DGKQ	ENST00000515182.1 linkuse as main transcript	c.107+138C>T	intron_variant	5		ENSP00000421756

Frequencies

GnomAD3 genomes

AF:

0.0134

AC:

2042

AN:

152136

Hom.:

Cov.:

show subpopulations

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.:

AF XY:

0.00302

AC XY:

381

AN XY:

125968

show subpopulations

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.:

Cov.:

AF XY:

0.00142

AC XY:

1014

AN XY:

714450

show subpopulations

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.:

Cov.:

AF XY:

0.0129

AC XY:

963

AN XY:

74454

show subpopulations

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.:

Bravo

AF:

0.0151

Asia WGS

AF:

0.00318

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Aug 15, 2017	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over