chr7-137552485-C-G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001321708.2(DGKI):​c.2031G>C​(p.Met677Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000889 in 1,461,840 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

DGKI
NM_001321708.2 missense

Scores

2
5
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.88
Variant links:
Genes affected
DGKI (HGNC:2855): (diacylglycerol kinase iota) This gene is a member of the type IV diacylglycerol kinase subfamily. Diacylglycerol kinases regulate the intracellular concentration of diacylglycerol through its phosphorylation, producing phosphatidic acid. The specific role of the enzyme encoded by this gene is undetermined, however, it may play a crucial role in the production of phosphatidic acid in the retina or in recessive forms of retinal degeneration. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DGKINM_001321708.2 linkc.2031G>C p.Met677Ile missense_variant Exon 20 of 33 ENST00000614521.2 NP_001308637.1 O75912A0A087WV00

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DGKIENST00000614521.2 linkc.2031G>C p.Met677Ile missense_variant Exon 20 of 33 5 NM_001321708.2 ENSP00000479053.2 A0A087WV00

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000889
AC:
13
AN:
1461840
Hom.:
0
Cov.:
31
AF XY:
0.00000963
AC XY:
7
AN XY:
727218
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33480
American (AMR)
AF:
0.00
AC:
0
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26136
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39700
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86256
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53420
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5762
European-Non Finnish (NFE)
AF:
0.0000117
AC:
13
AN:
1111970
Other (OTH)
AF:
0.00
AC:
0
AN:
60392
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.490
Heterozygous variant carriers
0
1
2
4
5
6
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
32

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Feb 28, 2023
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.2031G>C (p.M677I) alteration is located in exon 20 (coding exon 20) of the DGKI gene. This alteration results from a G to C substitution at nucleotide position 2031, causing the methionine (M) at amino acid position 677 to be replaced by an isoleucine (I). 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
Pathogenic
0.74
BayesDel_addAF
Benign
-0.071
T
BayesDel_noAF
Benign
-0.34
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Benign
0.088
.;T;T;.;T
Eigen
Benign
0.18
Eigen_PC
Uncertain
0.34
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.95
D;D;D;D;D
M_CAP
Benign
0.013
T
MetaRNN
Uncertain
0.59
D;D;D;D;D
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.9
.;M;.;.;.
PhyloP100
7.9
PrimateAI
Uncertain
0.64
T
PROVEAN
Benign
-1.6
N;N;N;N;.
REVEL
Benign
0.18
Sift
Benign
0.059
T;T;T;T;.
Sift4G
Benign
0.16
T;T;T;T;T
Polyphen
0.095
B;B;.;.;.
Vest4
0.55
MutPred
0.79
.;Gain of loop (P = 0.1069);Gain of loop (P = 0.1069);Gain of loop (P = 0.1069);.;
MVP
0.082
MPC
1.3
ClinPred
0.88
D
GERP RS
5.4
Varity_R
0.36
gMVP
0.61
Mutation Taster
=62/38
polymorphism

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

Other links and lift over

hg19: chr7-137237231; API