chr1-178833512-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_152663.5(RALGPS2):c.569T>C(p.Ile190Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000104 in 1,533,056 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000094 ( 0 hom. )
Consequence
RALGPS2
NM_152663.5 missense
NM_152663.5 missense
Scores
3
8
7
Clinical Significance
Conservation
PhyloP100: 7.56
Genes affected
RALGPS2 (HGNC:30279): (Ral GEF with PH domain and SH3 binding motif 2) Predicted to enable guanyl-nucleotide exchange factor activity. Predicted to be involved in regulation of Ral protein signal transduction; regulation of catalytic activity; and small GTPase mediated signal transduction. Predicted to be located in cytoplasm and plasma membrane. [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 |
---|---|---|---|---|---|---|---|
RALGPS2 | NM_152663.5 | c.569T>C | p.Ile190Thr | missense_variant | 8/20 | ENST00000367635.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RALGPS2 | ENST00000367635.8 | c.569T>C | p.Ile190Thr | missense_variant | 8/20 | 1 | NM_152663.5 | P3 | |
RALGPS2 | ENST00000367634.7 | c.569T>C | p.Ile190Thr | missense_variant | 8/19 | 2 | A1 | ||
RALGPS2 | ENST00000324778.5 | c.464T>C | p.Ile155Thr | missense_variant | 7/10 | 5 | |||
RALGPS2 | ENST00000495034.5 | n.907T>C | non_coding_transcript_exon_variant | 8/10 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152116Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000169 AC: 3AN: 177778Hom.: 0 AF XY: 0.0000204 AC XY: 2AN XY: 98208
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GnomAD4 exome AF: 0.00000941 AC: 13AN: 1380940Hom.: 0 Cov.: 30 AF XY: 0.00000583 AC XY: 4AN XY: 685560
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GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152116Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74320
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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 | Jun 06, 2023 | The c.569T>C (p.I190T) alteration is located in exon 8 (coding exon 7) of the RALGPS2 gene. This alteration results from a T to C substitution at nucleotide position 569, causing the isoleucine (I) at amino acid position 190 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
Cadd
Pathogenic
Dann
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
T
MetaRNN
Uncertain
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;L;.
MutationTaster
Benign
D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
D;D;D
REVEL
Uncertain
Sift
Benign
D;D;D
Sift4G
Benign
T;T;D
Polyphen
0.45
.;B;.
Vest4
MVP
MPC
0.80
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at