chr8-100038992-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_015668.5(RGS22):c.2105C>T(p.Ala702Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000248 in 1,612,610 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000026 ( 0 hom. )
Consequence
RGS22
NM_015668.5 missense
NM_015668.5 missense
Scores
1
6
12
Clinical Significance
Conservation
PhyloP100: 3.06
Genes affected
RGS22 (HGNC:24499): (regulator of G protein signaling 22) Enables G-protein alpha-subunit binding activity. Predicted to be involved in negative regulation of signal transduction. Located in actin cytoskeleton; cytosol; and fibrillar center. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RGS22 | NM_015668.5 | c.2105C>T | p.Ala702Val | missense_variant | 14/28 | ENST00000360863.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RGS22 | ENST00000360863.11 | c.2105C>T | p.Ala702Val | missense_variant | 14/28 | 1 | NM_015668.5 | P3 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152094Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000643 AC: 16AN: 248850Hom.: 0 AF XY: 0.000111 AC XY: 15AN XY: 135034
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GnomAD4 exome AF: 0.0000260 AC: 38AN: 1460516Hom.: 0 Cov.: 29 AF XY: 0.0000399 AC XY: 29AN XY: 726580
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GnomAD4 genome AF: 0.0000131 AC: 2AN: 152094Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74294
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 10, 2022 | The c.2105C>T (p.A702V) alteration is located in exon 14 (coding exon 14) of the RGS22 gene. This alteration results from a C to T substitution at nucleotide position 2105, causing the alanine (A) at amino acid position 702 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Benign
T;T;T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.;.;.
MutationTaster
Benign
N;N;N
PrimateAI
Uncertain
T
PROVEAN
Benign
N;.;N;N
REVEL
Benign
Sift
Benign
T;.;T;T
Sift4G
Uncertain
T;D;D;T
Polyphen
D;.;D;.
Vest4
MutPred
Gain of sheet (P = 0.0125);.;.;.;
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AG_spliceai
Position offset: 1
Find out detailed SpliceAI scores and Pangolin per-transcript scores at