chr7-100676163-CCTGCATCCCCCAGGCCTCGGGCCAGCGGCCAGGAG-C

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PVS1_StrongPM2

The NM_005273.4(GNB2):​c.-89-9_-64delATCCCCCAGGCCTCGGGCCAGCGGCCAGGAGCTGC variant causes a splice acceptor, splice region, 5 prime UTR, intron change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

GNB2
NM_005273.4 splice_acceptor, splice_region, 5_prime_UTR, intron

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.78
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 Likely_pathogenic. Variant got 6 ACMG points.

PVS1
Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.1427175 fraction of the gene. Cryptic splice site detected, with MaxEntScore 6.6, offset of 0 (no position change), new splice context is: gtcagccctgcctcccccAGccc. Cryptic site results in inframe change. If cryptic site found is not functional and variant results in exon loss, it results in frameshift change.
PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GNB2NM_005273.4 linkc.-89-9_-64delATCCCCCAGGCCTCGGGCCAGCGGCCAGGAGCTGC splice_region_variant Exon 2 of 10 ENST00000303210.9 NP_005264.2 P62879-1Q6FHM2
GNB2NM_005273.4 linkc.-89-9_-64delATCCCCCAGGCCTCGGGCCAGCGGCCAGGAGCTGC splice_acceptor_variant, splice_region_variant, 5_prime_UTR_variant, intron_variant Exon 2 of 10 ENST00000303210.9 NP_005264.2 P62879-1Q6FHM2
GNB2NM_005273.4 linkc.-89-9_-64delATCCCCCAGGCCTCGGGCCAGCGGCCAGGAGCTGC non_coding_transcript_variant ENST00000303210.9 NP_005264.2 P62879-1Q6FHM2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GNB2ENST00000303210.9 linkc.-89-9_-64delATCCCCCAGGCCTCGGGCCAGCGGCCAGGAGCTGC splice_region_variant Exon 2 of 10 1 NM_005273.4 ENSP00000305260.4 P62879-1
GNB2ENST00000303210 linkc.-89-9_-64delATCCCCCAGGCCTCGGGCCAGCGGCCAGGAGCTGC splice_acceptor_variant, splice_region_variant, 5_prime_UTR_variant, intron_variant Exon 2 of 10 1 NM_005273.4 ENSP00000305260.4 P62879-1
GNB2ENST00000303210.9 linkc.-89-9_-64delATCCCCCAGGCCTCGGGCCAGCGGCCAGGAGCTGC non_coding_transcript_variant 1 NM_005273.4 ENSP00000305260.4 P62879-1

Frequencies

GnomAD3 genomes
Cov.:
33
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
Cov.:
33

ClinVar

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

Submissions by phenotype

not provided Uncertain:1
Jan 31, 2024
GeneDx
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

Has not been previously published as pathogenic or benign to our knowledge; Canonical splice site variant in a gene for which loss-of-function is not a known mechanism of disease -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

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: chr7-100273786; API