chr16-89828618-C-G
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_032451.2(SPIRE2):āc.68C>Gā(p.Ser23Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000151 in 1,321,862 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.0000067 ( 0 hom., cov: 32)
Exomes š: 8.5e-7 ( 0 hom. )
Consequence
SPIRE2
NM_032451.2 missense
NM_032451.2 missense
Scores
2
6
11
Clinical Significance
Conservation
PhyloP100: 1.83
Genes affected
SPIRE2 (HGNC:30623): (spire type actin nucleation factor 2) Predicted to enable actin binding activity. Involved in establishment of meiotic spindle localization; formin-nucleated actin cable assembly; and positive regulation of double-strand break repair. Predicted to be located in cytoskeleton; cytosol; and plasma membrane. Predicted to be active in cell cortex and cytoplasmic vesicle membrane. Predicted to colocalize with cleavage furrow. [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 | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SPIRE2 | NM_032451.2 | c.68C>G | p.Ser23Cys | missense_variant | 1/15 | ENST00000378247.8 | NP_115827.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SPIRE2 | ENST00000378247.8 | c.68C>G | p.Ser23Cys | missense_variant | 1/15 | 1 | NM_032451.2 | ENSP00000367494 | P1 | |
SPIRE2 | ENST00000393062.6 | c.68C>G | p.Ser23Cys | missense_variant | 1/13 | 1 | ENSP00000376782 | |||
SPIRE2 | ENST00000563972.1 | c.68C>G | p.Ser23Cys | missense_variant | 1/3 | 1 | ENSP00000457940 | |||
SPIRE2 | ENST00000564878.5 | n.360+10080C>G | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes AF: 0.00000669 AC: 1AN: 149520Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 8.53e-7 AC: 1AN: 1172234Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 575986
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GnomAD4 genome AF: 0.00000668 AC: 1AN: 149628Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 72960
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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 | Dec 06, 2021 | The c.68C>G (p.S23C) alteration is located in exon 1 (coding exon 1) of the SPIRE2 gene. This alteration results from a C to G substitution at nucleotide position 68, causing the serine (S) at amino acid position 23 to be replaced by a cysteine (C). 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
Uncertain
DEOGEN2
Benign
.;T;.
Eigen
Uncertain
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T;D
M_CAP
Pathogenic
D
MetaRNN
Uncertain
D;D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M;.
MutationTaster
Benign
D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;N;D
REVEL
Uncertain
Sift
Benign
D;D;D
Sift4G
Benign
T;T;T
Polyphen
D;D;.
Vest4
MutPred
Gain of catalytic residue at L24 (P = 0.0103);Gain of catalytic residue at L24 (P = 0.0103);Gain of catalytic residue at L24 (P = 0.0103);
MVP
MPC
0.65
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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
Publications
No publications associated with this variant yet.