16-89853617-C-T

Variant names:

• chr16-89853617-C-T
• rs8060934
• NM_032451.2:c.646-669C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 17 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032451.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPIRE2	NM_032451.2	MANE Select	c.646-669C>T		intron	N/A	NP_115827.1	Q8WWL2-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPIRE2	ENST00000378247.8	TSL:1 MANE Select	c.646-669C>T		intron	N/A	ENSP00000367494.3	Q8WWL2-1
	SPIRE2	ENST00000393062.6	TSL:1	c.646-669C>T		intron	N/A	ENSP00000376782.2	Q8WWL2-2
	SPIRE2	ENST00000569108.5	TSL:1	n.796-669C>T		intron	N/A

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

African (AFR) AF: 0.543 AC: 22462 AN: 41350

American (AMR) AF: 0.613 AC: 9345 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.456 AC: 1579 AN: 3460

East Asian (EAS) AF: 0.755 AC: 3860 AN: 5114

South Asian (SAS) AF: 0.675 AC: 3250 AN: 4816

European-Finnish (FIN) AF: 0.611 AC: 6430 AN: 10532

Middle Eastern (MID) AF: 0.541 AC: 159 AN: 294

European-Non Finnish (NFE) AF: 0.527 AC: 35760 AN: 67852

Other (OTH) AF: 0.534 AC: 1123 AN: 2104

Alfa AF: 0.529 Hom.: 38873

Bravo AF: 0.557

Asia WGS AF: 0.707 AC: 2462 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.11
DANN	Benign	0.91
PhyloP100		-1.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs8060934; hg19: chr16-89920025;