chr16-89828663-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_032451.2(SPIRE2):ā€‹c.113A>Gā€‹(p.Glu38Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000000816 in 1,225,580 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 8.2e-7 ( 0 hom. )

Consequence

SPIRE2
NM_032451.2 missense

Scores

5
10
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.83
Variant links:
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
SPIRE2NM_032451.2 linkuse as main transcriptc.113A>G p.Glu38Gly missense_variant 1/15 ENST00000378247.8 NP_115827.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SPIRE2ENST00000378247.8 linkuse as main transcriptc.113A>G p.Glu38Gly missense_variant 1/151 NM_032451.2 ENSP00000367494 P1Q8WWL2-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
8.16e-7
AC:
1
AN:
1225580
Hom.:
0
Cov.:
31
AF XY:
0.00000165
AC XY:
1
AN XY:
605022
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000101
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

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 submitterclinical testingAmbry GeneticsMay 03, 2023The c.113A>G (p.E38G) alteration is located in exon 1 (coding exon 1) of the SPIRE2 gene. This alteration results from a A to G substitution at nucleotide position 113, causing the glutamic acid (E) at amino acid position 38 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.96
BayesDel_addAF
Uncertain
0.094
D
BayesDel_noAF
Benign
-0.10
CADD
Pathogenic
33
DANN
Uncertain
1.0
DEOGEN2
Benign
0.29
.;T;.
Eigen
Uncertain
0.42
Eigen_PC
Uncertain
0.33
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Uncertain
0.97
D;D;D
M_CAP
Pathogenic
0.93
D
MetaRNN
Uncertain
0.50
D;D;D
MetaSVM
Benign
-0.77
T
MutationAssessor
Pathogenic
3.1
M;M;.
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Pathogenic
0.94
D
PROVEAN
Uncertain
-3.7
D;D;D
REVEL
Uncertain
0.32
Sift
Uncertain
0.0010
D;D;D
Sift4G
Pathogenic
0.0
D;D;D
Polyphen
0.98
D;D;.
Vest4
0.42
MutPred
0.51
Loss of stability (P = 0.0521);Loss of stability (P = 0.0521);Loss of stability (P = 0.0521);
MVP
0.63
MPC
0.72
ClinPred
0.93
D
GERP RS
2.9
Varity_R
0.59
gMVP
0.55

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.11
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1189423392; hg19: chr16-89895071; API