Variant chr16-89828677-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_032451.2(SPIRE2):c.127G>A(p.Val43Met) variant causes a missense change. The variant allele was found at a frequency of 0.00031 in 1,340,182 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00033 ( 0 hom. )

Consequence

SPIRE2
NM_032451.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.30

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]

SPIRE2 links:

Genome browser will be placed here

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
SPIRE2	NM_032451.2 linkuse as main transcript	c.127G>A	p.Val43Met	missense_variant	1/15	ENST00000378247.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPIRE2	ENST00000378247.8 linkuse as main transcript	c.127G>A	p.Val43Met	missense_variant	1/15	1	NM_032451.2	P1	Q8WWL2-1

Frequencies

GnomAD3 genomes

AF:

0.000146

AC:

AN:

150436

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000727

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000661

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000267

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000330

AC:

393

AN:

1189746

Hom.:

Cov.:

AF XY:

0.000319

AC XY:

186

AN XY:

583910

show subpopulations

Gnomad4 AFR exome

AF:

0.0000397

Gnomad4 AMR exome

AF:

0.0000835

Gnomad4 ASJ exome

AF:

0.000109

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000412

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000387

Gnomad4 OTH exome

AF:

0.000195

GnomAD4 genome

AF:

0.000146

AC:

AN:

150436

Hom.:

Cov.:

AF XY:

0.000109

AC XY:

AN XY:

73400

show subpopulations

Gnomad4 AFR

AF:

0.0000727

Gnomad4 AMR

AF:

0.0000661

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000267

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000485

Hom.:

Bravo

AF:

0.000174

ExAC

AF:

0.000109

AC:

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

Aug 02, 2022

The c.127G>A (p.V43M) alteration is located in exon 1 (coding exon 1) of the SPIRE2 gene. This alteration results from a G to A substitution at nucleotide position 127, causing the valine (V) at amino acid position 43 to be replaced by a methionine (M). 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

0.71

BayesDel_addAF

Benign

-0.041

BayesDel_noAF

Benign

-0.30

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.051

.;T;.

Eigen

Benign

0.16

Eigen_PC

Benign

0.076

FATHMM_MKL

Uncertain

0.83

LIST_S2

Uncertain

0.96

D;D;D

M_CAP

Pathogenic

0.90

MetaRNN

Uncertain

0.53

D;D;D

MetaSVM

Benign

-0.91

MutationAssessor

Uncertain

2.6

M;M;.

MutationTaster

Benign

0.97

D;D;D

PrimateAI

Pathogenic

0.96

PROVEAN

Benign

-1.3

N;N;N

REVEL

Benign

0.22

Sift

Benign

0.084

T;T;T

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

1.0

D;D;.

Vest4

0.57

MutPred

0.66

Gain of disorder (P = 0.0746);Gain of disorder (P = 0.0746);Gain of disorder (P = 0.0746);

MVP

0.53

MPC

0.66

ClinPred

0.27

GERP RS

1.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.071

gMVP

0.40

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over