Genetic Variant GBP2:p.Glu334Gln (chr1-89114165-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_004120.5(GBP2):c.1000G>C(p.Glu334Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E334K) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

GBP2
NM_004120.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.723

Publications

0 publications found

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]

GBP2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.118820846).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004120.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GBP2	NM_004120.5	MANE Select	c.1000G>C	p.Glu334Gln	missense	Exon 7 of 11	NP_004111.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GBP2	ENST00000370466.4	TSL:1 MANE Select	c.1000G>C	p.Glu334Gln	missense	Exon 7 of 11	ENSP00000359497.3	P32456
GBP2	ENST00000875570.1		c.1000G>C	p.Glu334Gln	missense	Exon 7 of 11	ENSP00000545629.1
GBP2	ENST00000875572.1		c.1000G>C	p.Glu334Gln	missense	Exon 6 of 10	ENSP00000545631.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461892

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727248

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33478

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1112012

Other (OTH)

AF:

0.0000166

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.69

CADD

Benign

9.8

(source)

DANN

Benign

0.87

DEOGEN2

Benign

0.068

Eigen

Benign

-0.89

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.015

LIST_S2

Benign

0.33

M_CAP

Benign

0.0027

MetaRNN

Benign

0.12

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.8

PhyloP100

-0.72

PrimateAI

Benign

0.31

PROVEAN

Benign

-2.2

REVEL

Benign

0.029

Sift

Benign

0.17

Sift4G

Benign

0.53

Polyphen

0.61

Vest4

0.079

MutPred

0.48

Loss of phosphorylation at Y333 (P = 0.2148)

MVP

0.17

MPC

0.11

ClinPred

0.70

GERP RS

-1.9

Varity_R

0.092

gMVP

0.12

Mutation Taster

=93/7

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over