2-168900844-C-T

Variant names:

• chr2-168900844-C-T
• rs1402837
• ENST00000861849.1:c.-172-10158G>A

Variant summary

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

The ENST00000451987.5(SPC25):​c.-172-10158G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.253 in 151,894 control chromosomes in the GnomAD database, including 5,074 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 0.25 (5074 hom., cov: 32)
• Consequence: SPC25 ENST00000451987.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.140
• Publications: 44 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.382 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPC25	ENST00000861849.1		c.-172-10158G>A		intron	N/A	ENSP00000531908.1
	SPC25	ENST00000861850.1		c.-14-11311G>A		intron	N/A	ENSP00000531909.1
	SPC25	ENST00000451987.5	TSL:3	c.-172-10158G>A		intron	N/A	ENSP00000393322.1	C9JW94

Frequencies

GnomAD3 genomes AF: 0.253 AC: 38325 AN: 151772 Hom.: 5070 Cov.: 32

Gnomad AFR AF: 0.306

Gnomad AMI AF: 0.421

Gnomad AMR AF: 0.213

Gnomad ASJ AF: 0.246

Gnomad EAS AF: 0.396

Gnomad SAS AF: 0.224

Gnomad FIN AF: 0.177

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.230

Gnomad OTH AF: 0.255

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

GnomAD4 genome AF: 0.253 AC: 38364 AN: 151894 Hom.: 5074 Cov.: 32 AF XY: 0.251 AC XY: 18635 AN XY: 74224

African (AFR) AF: 0.306 AC: 12676 AN: 41400

American (AMR) AF: 0.212 AC: 3240 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.246 AC: 851 AN: 3466

East Asian (EAS) AF: 0.396 AC: 2046 AN: 5164

South Asian (SAS) AF: 0.225 AC: 1080 AN: 4808

European-Finnish (FIN) AF: 0.177 AC: 1860 AN: 10528

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.230 AC: 15622 AN: 67952

Other (OTH) AF: 0.257 AC: 542 AN: 2112

Alfa AF: 0.238 Hom.: 15742

Bravo AF: 0.257

Asia WGS AF: 0.282 AC: 978 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.8
DANN	Benign	0.43
PhyloP100		-0.14
PromoterAI		0.0041	Neutral

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1402837;

hg19: chr2-169757354;