7-100677501-C-G

Variant names:

• chr7-100677501-C-G
• NM_005273.4:c.271C>G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_005273.4(GNB2):​c.271C>G​(p.His91Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.83

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.872

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GNB2	NM_005273.4	c.271C>G	p.His91Asp	missense_variant	Exon 6 of 10	ENST00000303210.9	NP_005264.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GNB2	ENST00000303210.9	c.271C>G	p.His91Asp	missense_variant	Exon 6 of 10	1	NM_005273.4	ENSP00000305260.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Aug 07, 2024

GeneDx

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.42	D
BayesDel_noAF	Pathogenic	0.36
CADD	Uncertain	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.29	T;.;T;T;T;T;.;T
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	.;D;.;D;.;D;D;D
M_CAP	Uncertain	0.27	D
MetaRNN	Pathogenic	0.87	D;D;D;D;D;D;D;D
MetaSVM	Uncertain	0.37	D
MutationAssessor	Uncertain	2.6	M;.;.;.;M;.;.;M
PrimateAI	Pathogenic	0.90	D
PROVEAN	Pathogenic	-7.0	D;D;D;D;D;D;D;D
REVEL	Uncertain	0.54
Sift	Uncertain	0.0010	D;D;D;D;D;D;D;D
Sift4G	Uncertain	0.0050	D;D;D;D;D;D;D;D
Polyphen		0.29	B;.;.;.;B;.;.;B
Vest4		0.89
MutPred		0.59		Loss of methylation at K89 (P = 0.0679);Loss of methylation at K89 (P = 0.0679);.;.;Loss of methylation at K89 (P = 0.0679);Loss of methylation at K89 (P = 0.0679);Loss of methylation at K89 (P = 0.0679);Loss of methylation at K89 (P = 0.0679);
MVP		0.91
MPC		1.9
ClinPred		0.99	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.82
gMVP		0.88

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: chr7-100275124;