19-1969857-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001319.7(CSNK1G2):​c.85G>A​(p.Gly29Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000648 in 1,311,408 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000068 ( 0 hom. )

Consequence

CSNK1G2
NM_001319.7 missense

Scores

1
18

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.654
Variant links:
Genes affected
CSNK1G2 (HGNC:2455): (casein kinase 1 gamma 2) Enables protein serine/threonine kinase activity. Involved in peptidyl-serine phosphorylation. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.05893621).
BP6
Variant 19-1969857-G-A is Benign according to our data. Variant chr19-1969857-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2507719.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High AC in GnomAd4 at 6 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CSNK1G2NM_001319.7 linkuse as main transcriptc.85G>A p.Gly29Ser missense_variant 2/12 ENST00000255641.13

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CSNK1G2ENST00000255641.13 linkuse as main transcriptc.85G>A p.Gly29Ser missense_variant 2/121 NM_001319.7 P1
CSNK1G2ENST00000589385.5 linkuse as main transcriptc.34G>A p.Gly12Ser missense_variant 1/65
CSNK1G2ENST00000589350.2 linkuse as main transcriptc.85G>A p.Gly29Ser missense_variant 4/55
CSNK1G2ENST00000591752.5 linkuse as main transcriptc.85G>A p.Gly29Ser missense_variant 2/35

Frequencies

GnomAD3 genomes
AF:
0.0000394
AC:
6
AN:
152252
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000588
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000422
AC:
5
AN:
118418
Hom.:
0
AF XY:
0.0000156
AC XY:
1
AN XY:
64016
show subpopulations
Gnomad AFR exome
AF:
0.000105
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000381
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000158
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000682
AC:
79
AN:
1159156
Hom.:
0
Cov.:
30
AF XY:
0.0000649
AC XY:
36
AN XY:
554952
show subpopulations
Gnomad4 AFR exome
AF:
0.0000803
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000164
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000724
Gnomad4 OTH exome
AF:
0.0000648
GnomAD4 genome
AF:
0.0000394
AC:
6
AN:
152252
Hom.:
0
Cov.:
32
AF XY:
0.0000538
AC XY:
4
AN XY:
74378
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000588
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000670
Hom.:
0
Bravo
AF:
0.0000604
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000432
AC:
5

ClinVar

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

Submissions by phenotype

not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingAmbry GeneticsApr 10, 2023This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.069
BayesDel_addAF
Benign
-0.43
T
BayesDel_noAF
Benign
-0.54
CADD
Benign
13
DANN
Uncertain
0.97
DEOGEN2
Benign
0.096
T;.;.
Eigen
Benign
-0.55
Eigen_PC
Benign
-0.48
FATHMM_MKL
Benign
0.69
D
LIST_S2
Benign
0.76
T;T;T
M_CAP
Benign
0.023
T
MetaRNN
Benign
0.059
T;T;T
MetaSVM
Benign
-0.93
T
MutationAssessor
Benign
0.32
N;.;.
MutationTaster
Benign
0.52
N
PrimateAI
Benign
0.36
T
PROVEAN
Benign
-0.37
N;.;.
REVEL
Benign
0.083
Sift
Benign
0.21
T;.;.
Sift4G
Benign
1.0
T;T;T
Polyphen
0.57
P;.;.
Vest4
0.17
MVP
0.38
MPC
0.28
ClinPred
0.051
T
GERP RS
-0.39
RBP_binding_hub_radar
0.92
RBP_regulation_power_radar
2.7
Varity_R
0.023
gMVP
0.22

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: rs371407393; hg19: chr19-1969856; API