NM_032451.2:c.646-669C>A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_032451.2(SPIRE2):​c.646-669C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).

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

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

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes Cov.: 30

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

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 38873

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.044
DANN	Benign	0.86
PhyloP100		-1.4
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

Other links and lift over

dbSNP: rs8060934; hg19: chr16-89920025;