chr2-168900844-C-T

Position:

• chr2-168900844-C-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPC25	ENST00000451987.5	c.-172-10158G>A		intron_variant		3		ENSP00000393322
SPC25	ENST00000472216.2	n.177-10158G>A		intron_variant, non_coding_transcript_variant		5

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

Gnomad4 AFR AF: 0.306

Gnomad4 AMR AF: 0.212

Gnomad4 ASJ AF: 0.246

Gnomad4 EAS AF: 0.396

Gnomad4 SAS AF: 0.225

Gnomad4 FIN AF: 0.177

Gnomad4 NFE AF: 0.230

Gnomad4 OTH AF: 0.257

Alfa AF: 0.232 Hom.: 5362

Bravo AF: 0.257

Asia WGS AF: 0.282 AC: 978 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.8
DANN	Benign	0.43

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1402837; hg19: chr2-169757354;