chr4-961844-G-A

Position:

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

2
Splicing: ADA: 0.00001241
2

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]

Genome browser will be placed here

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 HGVSp Effect #exon/exons MANE Protein UniProt
DGKQNM_001347.4 linkuse as main transcriptc.2316-10C>T splice_polypyrimidine_tract_variant, intron_variant ENST00000273814.8 NP_001338.2
DGKQXM_011513411.2 linkuse as main transcriptc.2316-10C>T splice_polypyrimidine_tract_variant, intron_variant XP_011511713.1
DGKQXM_047449687.1 linkuse as main transcriptc.2403-10C>T splice_polypyrimidine_tract_variant, intron_variant XP_047305643.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
DGKQENST00000273814.8 linkuse as main transcriptc.2316-10C>T splice_polypyrimidine_tract_variant, intron_variant 1 NM_001347.4 ENSP00000273814 P1
DGKQENST00000509465.5 linkuse as main transcriptc.2117-10C>T splice_polypyrimidine_tract_variant, intron_variant 5 ENSP00000425862
DGKQENST00000515182.1 linkuse as main transcriptc.107+138C>T intron_variant 5 ENSP00000421756

Frequencies

GnomAD3 genomes
AF:
0.0134
AC:
2042
AN:
152136
Hom.:
45
Cov.:
33
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.:
16
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.:
47
Cov.:
34
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.:
47
Cov.:
33
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.:
11
Bravo
AF:
0.0151
Asia WGS
AF:
0.00318
AC:
11
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 submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpAug 15, 2017- -
Benign, criteria provided, single submitternot providedBreakthrough 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.

Other links and lift over

dbSNP: rs77865682; hg19: chr4-955632; API