rs524586

Variant names:

• chr2-168881341-A-G
• rs524586
• NM_020675.4:c.200-3957T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020675.4(SPC25):​c.200-3957T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.57 in 152,064 control chromosomes in the GnomAD database, including 25,238 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 0.57 (25238 hom., cov: 32)
• Consequence: SPC25 NM_020675.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0830
• Publications: 8 publications found

Genes affected

SPC25 (HGNC:24031): (SPC25 component of NDC80 kinetochore complex) This gene encodes a protein that may be involved in kinetochore-microtubule interaction and spindle checkpoint activity. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.68 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020675.4. 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
	SPC25	NM_020675.4	MANE Select	c.200-3957T>C		intron	N/A	NP_065726.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPC25	ENST00000282074.7	TSL:1 MANE Select	c.200-3957T>C		intron	N/A	ENSP00000282074.2
	SPC25	ENST00000451987.5	TSL:3	c.200-3957T>C		intron	N/A	ENSP00000393322.1
	SPC25	ENST00000472216.2	TSL:5	n.607+3507T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.570 AC: 86555 AN: 151946 Hom.: 25200 Cov.: 32

Gnomad AFR AF: 0.687

Gnomad AMI AF: 0.577

Gnomad AMR AF: 0.571

Gnomad ASJ AF: 0.556

Gnomad EAS AF: 0.619

Gnomad SAS AF: 0.660

Gnomad FIN AF: 0.498

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.501

Gnomad OTH AF: 0.547

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

GnomAD4 genome AF: 0.570 AC: 86642 AN: 152064 Hom.: 25238 Cov.: 32 AF XY: 0.574 AC XY: 42647 AN XY: 74352

African (AFR) AF: 0.687 AC: 28486 AN: 41468

American (AMR) AF: 0.572 AC: 8735 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.556 AC: 1925 AN: 3464

East Asian (EAS) AF: 0.619 AC: 3196 AN: 5166

South Asian (SAS) AF: 0.658 AC: 3175 AN: 4822

European-Finnish (FIN) AF: 0.498 AC: 5261 AN: 10570

Middle Eastern (MID) AF: 0.558 AC: 164 AN: 294

European-Non Finnish (NFE) AF: 0.501 AC: 34023 AN: 67972

Other (OTH) AF: 0.544 AC: 1152 AN: 2116

Alfa AF: 0.535 Hom.: 19341

Bravo AF: 0.580

Asia WGS AF: 0.659 AC: 2292 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.4
DANN	Benign	0.72
PhyloP100		0.083
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: rs524586; hg19: chr2-169737851;