rs2232316

Positions:

• chr2-168901052-G-A
• chr2-168901052-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000451987.5(SPC25):​c.-172-10366C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 152,210 control chromosomes in the GnomAD database, including 919 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 0.11 (919 hom., cov: 33)
• Consequence: SPC25 ENST00000451987.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.06

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=-0.63).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.137 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.-172-10366C>T		intron_variant		3		ENSP00000393322
SPC25	ENST00000472216.2	n.177-10366C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16705 AN: 152092 Hom.: 920 Cov.: 33

Gnomad AFR AF: 0.133

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.141

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.116

Gnomad SAS AF: 0.0533

Gnomad FIN AF: 0.0576

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.101

Gnomad OTH AF: 0.124

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

GnomAD4 genome AF: 0.110 AC: 16734 AN: 152210 Hom.: 919 Cov.: 33 AF XY: 0.107 AC XY: 7939 AN XY: 74424

Gnomad4 AFR AF: 0.133

Gnomad4 AMR AF: 0.142

Gnomad4 ASJ AF: 0.115

Gnomad4 EAS AF: 0.116

Gnomad4 SAS AF: 0.0539

Gnomad4 FIN AF: 0.0576

Gnomad4 NFE AF: 0.101

Gnomad4 OTH AF: 0.125

Alfa AF: 0.102 Hom.: 678

Bravo AF: 0.123

Asia WGS AF: 0.103 AC: 359 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	14
DANN	Benign	0.55

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2232316; hg19: chr2-169757562;