7-100676700-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_005273.4(GNB2):​c.104C>T​(p.Ala35Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

GNB2
NM_005273.4 missense

Scores

1
5
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.17
Variant links:
Genes affected
GNB2 (HGNC:4398): (G protein subunit beta 2) Heterotrimeric guanine nucleotide-binding proteins (G proteins), which integrate signals between receptors and effector proteins, are composed of an alpha, a beta, and a gamma subunit. These subunits are encoded by families of related genes. This gene encodes a beta subunit. Beta subunits are important regulators of alpha subunits, as well as of certain signal transduction receptors and effectors. This gene contains a trinucleotide (CCG) repeat length polymorphism in its 5' UTR. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.32425117).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GNB2NM_005273.4 linkc.104C>T p.Ala35Val missense_variant Exon 4 of 10 ENST00000303210.9 NP_005264.2 P62879-1Q6FHM2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GNB2ENST00000303210.9 linkc.104C>T p.Ala35Val missense_variant Exon 4 of 10 1 NM_005273.4 ENSP00000305260.4 P62879-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
33

ClinVar

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

Submissions by phenotype

Inborn genetic diseases Uncertain:1
Jan 02, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.104C>T (p.A35V) alteration is located in exon 4 (coding exon 3) of the GNB2 gene. This alteration results from a C to T substitution at nucleotide position 104, causing the alanine (A) at amino acid position 35 to be replaced by a valine (V). 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
0.11
BayesDel_addAF
Benign
-0.15
T
BayesDel_noAF
Benign
-0.45
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Benign
0.094
T;.;T;T;.;T
Eigen
Uncertain
0.20
Eigen_PC
Uncertain
0.34
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.92
.;D;.;D;D;D
M_CAP
Benign
0.010
T
MetaRNN
Benign
0.32
T;T;T;T;T;T
MetaSVM
Benign
-0.96
T
MutationAssessor
Benign
1.9
L;.;L;.;.;L
PrimateAI
Uncertain
0.59
T
PROVEAN
Benign
-1.8
N;N;N;N;N;N
REVEL
Benign
0.13
Sift
Benign
0.050
D;T;D;D;T;D
Sift4G
Benign
0.18
T;T;T;T;T;T
Polyphen
0.0010
B;.;B;.;.;B
Vest4
0.38
MutPred
0.38
Loss of disorder (P = 0.0683);Loss of disorder (P = 0.0683);Loss of disorder (P = 0.0683);Loss of disorder (P = 0.0683);Loss of disorder (P = 0.0683);Loss of disorder (P = 0.0683);
MVP
0.22
MPC
1.2
ClinPred
0.95
D
GERP RS
5.0
Varity_R
0.23
gMVP
0.82

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-100274323; API