2-168901031-G-A

Variant names:

• chr2-168901031-G-A
• rs573225
• ENST00000451987.5:c.-172-10345C>T

Variant summary

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

The ENST00000451987.5(SPC25):​c.-172-10345C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.778 in 152,224 control chromosomes in the GnomAD database, including 46,938 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 0.78 (46938 hom., cov: 33)
• Consequence: SPC25 ENST00000451987.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.69
• Publications: 24 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=-0.48).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.913 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000451987.5. 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

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPC25	ENST00000451987.5	TSL:3	c.-172-10345C>T		intron	N/A	ENSP00000393322.1
	SPC25	ENST00000472216.2	TSL:5	n.177-10345C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.778 AC: 118274 AN: 152106 Hom.: 46875 Cov.: 33

Gnomad AFR AF: 0.921

Gnomad AMI AF: 0.773

Gnomad AMR AF: 0.790

Gnomad ASJ AF: 0.767

Gnomad EAS AF: 0.931

Gnomad SAS AF: 0.830

Gnomad FIN AF: 0.703

Gnomad MID AF: 0.731

Gnomad NFE AF: 0.685

Gnomad OTH AF: 0.767

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

GnomAD4 genome AF: 0.778 AC: 118398 AN: 152224 Hom.: 46938 Cov.: 33 AF XY: 0.782 AC XY: 58154 AN XY: 74404

African (AFR) AF: 0.921 AC: 38285 AN: 41570

American (AMR) AF: 0.790 AC: 12083 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.767 AC: 2659 AN: 3468

East Asian (EAS) AF: 0.930 AC: 4823 AN: 5184

South Asian (SAS) AF: 0.830 AC: 4002 AN: 4824

European-Finnish (FIN) AF: 0.703 AC: 7436 AN: 10576

Middle Eastern (MID) AF: 0.745 AC: 219 AN: 294

European-Non Finnish (NFE) AF: 0.685 AC: 46570 AN: 67994

Other (OTH) AF: 0.765 AC: 1618 AN: 2114

Alfa AF: 0.715 Hom.: 80884

Bravo AF: 0.792

Asia WGS AF: 0.857 AC: 2981 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	16
DANN	Benign	0.51
PhyloP100		1.7
PromoterAI		-0.0063	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs573225; hg19: chr2-169757541;