1-89108225-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_004120.5(GBP2):​c.1726G>A​(p.Asp576Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000638 in 1,613,350 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000066 ( 0 hom. )

Consequence

GBP2
NM_004120.5 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -5.01
Variant links:
Genes affected
GBP2 (HGNC:4183): (guanylate binding protein 2) This gene belongs to the guanine-binding protein (GBP) family, which includes interferon-induced proteins that can bind to guanine nucleotides (GMP, GDP and GTP). The encoded protein is a GTPase which hydrolyzes GTP, predominantly to GDP. The protein may play a role as a marker of squamous cell carcinomas. [provided by RefSeq, Jul 2013]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.04416108).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GBP2NM_004120.5 linkc.1726G>A p.Asp576Asn missense_variant Exon 11 of 11 ENST00000370466.4 NP_004111.2 P32456Q8TCE5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GBP2ENST00000370466.4 linkc.1726G>A p.Asp576Asn missense_variant Exon 11 of 11 1 NM_004120.5 ENSP00000359497.3 P32456
GBP2ENST00000464839.5 linkn.1726G>A non_coding_transcript_exon_variant Exon 14 of 15 2 ENSP00000434282.1 P32456
GBP2ENST00000493802.5 linkn.686G>A non_coding_transcript_exon_variant Exon 5 of 5 3

Frequencies

GnomAD3 genomes
AF:
0.0000394
AC:
6
AN:
152156
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.0000882
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000279
AC:
7
AN:
251246
Hom.:
0
AF XY:
0.0000368
AC XY:
5
AN XY:
135798
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000616
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000664
AC:
97
AN:
1461194
Hom.:
0
Cov.:
29
AF XY:
0.0000743
AC XY:
54
AN XY:
726940
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000837
Gnomad4 OTH exome
AF:
0.0000497
GnomAD4 genome
AF:
0.0000394
AC:
6
AN:
152156
Hom.:
0
Cov.:
32
AF XY:
0.0000538
AC XY:
4
AN XY:
74324
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000882
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000113
Hom.:
0
Bravo
AF:
0.0000378
ExAC
AF:
0.0000247
AC:
3
EpiCase
AF:
0.000164
EpiControl
AF:
0.0000593

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Sep 20, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1726G>A (p.D576N) alteration is located in exon 11 (coding exon 10) of the GBP2 gene. This alteration results from a G to A substitution at nucleotide position 1726, causing the aspartic acid (D) at amino acid position 576 to be replaced by an asparagine (N). 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
Benign
0.081
BayesDel_addAF
Benign
-0.48
T
BayesDel_noAF
Benign
-0.74
CADD
Benign
0.0020
DANN
Benign
0.58
DEOGEN2
Benign
0.028
T
Eigen
Benign
-1.7
Eigen_PC
Benign
-1.8
FATHMM_MKL
Benign
0.0038
N
LIST_S2
Benign
0.45
T
M_CAP
Benign
0.0068
T
MetaRNN
Benign
0.044
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
-0.49
N
PrimateAI
Benign
0.33
T
PROVEAN
Benign
-0.010
N
REVEL
Benign
0.049
Sift
Benign
0.62
T
Sift4G
Benign
0.60
T
Polyphen
0.0
B
Vest4
0.13
MutPred
0.48
Loss of ubiquitination at K572 (P = 0.0315);
MVP
0.25
MPC
0.093
ClinPred
0.032
T
GERP RS
-5.0
Varity_R
0.022
gMVP
0.11

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: rs766975415; hg19: chr1-89573908; API