16-89853617-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032451.2(SPIRE2):c.646-669C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.557 in 151,668 control chromosomes in the GnomAD database, including 23,857 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.56 (23857 hom., cov: 30)
• Consequence: SPIRE2 NM_032451.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.35

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.735 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPIRE2	NM_032451.2	c.646-669C>T		intron_variant		ENST00000378247.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPIRE2	ENST00000378247.8	c.646-669C>T		intron_variant		1	NM_032451.2	P1
SPIRE2	ENST00000393062.6	c.646-669C>T		intron_variant		1
SPIRE2	ENST00000569108.5	n.796-669C>T		intron_variant, non_coding_transcript_variant		1
SPIRE2	ENST00000566337.5	c.*595-669C>T		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.556 AC: 84337 AN: 151550 Hom.: 23836 Cov.: 30

Gnomad AFR AF: 0.543

Gnomad AMI AF: 0.480

Gnomad AMR AF: 0.613

Gnomad ASJ AF: 0.456

Gnomad EAS AF: 0.756

Gnomad SAS AF: 0.677

Gnomad FIN AF: 0.611

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.527

Gnomad OTH AF: 0.533

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.557 AC: 84405 AN: 151668 Hom.: 23857 Cov.: 30 AF XY: 0.567 AC XY: 42040 AN XY: 74086

Gnomad4 AFR AF: 0.543

Gnomad4 AMR AF: 0.613

Gnomad4 ASJ AF: 0.456

Gnomad4 EAS AF: 0.755

Gnomad4 SAS AF: 0.675

Gnomad4 FIN AF: 0.611

Gnomad4 NFE AF: 0.527

Gnomad4 OTH AF: 0.534

Alfa AF: 0.523 Hom.: 27100

Bravo AF: 0.557

Asia WGS AF: 0.707 AC: 2462 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.11
Dann	Benign	0.91
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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

Other links and lift over

dbSNP: rs8060934; hg19: chr16-89920025;