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GeneBe

4-962459-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_001347.4(DGKQ):c.2190C>T(p.Asp730=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00116 in 1,596,394 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0066 ( 12 hom., cov: 34)
Exomes 𝑓: 0.00059 ( 12 hom. )

Consequence

DGKQ
NM_001347.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.892
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 -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.89).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 4-962459-G-A is Benign according to our data. Variant chr4-962459-G-A is described in ClinVar as [Benign]. Clinvar id is 775936.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.892 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00656 (999/152332) while in subpopulation AFR AF= 0.0218 (907/41582). AF 95% confidence interval is 0.0206. There are 12 homozygotes in gnomad4. There are 466 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 12 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
DGKQNM_001347.4 linkuse as main transcriptc.2190C>T p.Asp730= synonymous_variant 18/23 ENST00000273814.8
DGKQXM_047449687.1 linkuse as main transcriptc.2277C>T p.Asp759= synonymous_variant 18/23
DGKQXM_011513411.2 linkuse as main transcriptc.2190C>T p.Asp730= synonymous_variant 18/23

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
DGKQENST00000273814.8 linkuse as main transcriptc.2190C>T p.Asp730= synonymous_variant 18/231 NM_001347.4 P1
DGKQENST00000509465.5 linkuse as main transcriptc.1992C>T p.Asp664= synonymous_variant 17/225
DGKQENST00000515182.1 linkuse as main transcript upstream_gene_variant 5

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00657
AC:
1000
AN:
152214
Hom.:
12
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.0219
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00504
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000735
Gnomad OTH
AF:
0.00430
GnomAD3 exomes
AF:
0.00157
AC:
354
AN:
226086
Hom.:
4
AF XY:
0.00113
AC XY:
139
AN XY:
123286
show subpopulations
Gnomad AFR exome
AF:
0.0223
Gnomad AMR exome
AF:
0.000697
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000105
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000581
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000591
AC:
853
AN:
1444062
Hom.:
12
Cov.:
32
AF XY:
0.000488
AC XY:
350
AN XY:
717862
show subpopulations
Gnomad4 AFR exome
AF:
0.0202
Gnomad4 AMR exome
AF:
0.00120
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000473
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000271
Gnomad4 OTH exome
AF:
0.00152
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00656
AC:
999
AN:
152332
Hom.:
12
Cov.:
34
AF XY:
0.00626
AC XY:
466
AN XY:
74500
show subpopulations
Gnomad4 AFR
AF:
0.0218
Gnomad4 AMR
AF:
0.00503
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000735
Gnomad4 OTH
AF:
0.00426
Alfa
AF:
0.00334
Hom.:
3
Bravo
AF:
0.00799
Asia WGS
AF:
0.000577
AC:
2
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeAug 15, 2017- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.89
Cadd
Benign
0.23
Dann
Benign
0.63
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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

LitVar

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

Other links and lift over

dbSNP: rs11946829; hg19: chr4-956247; API