rs13431652

Positions:

• chr2-168896905-T-C

Variant summary

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

The ENST00000451987.5(SPC25):​c.-172-6219A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 152,068 control chromosomes in the GnomAD database, including 4,880 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 0.24 (4880 hom., cov: 31)
• Consequence: SPC25 ENST00000451987.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.299

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.304 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.-172-6219A>G		intron_variant		3		ENSP00000393322
SPC25	ENST00000472216.2	n.177-6219A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.243 AC: 36884 AN: 151950 Hom.: 4880 Cov.: 31

Gnomad AFR AF: 0.170

Gnomad AMI AF: 0.222

Gnomad AMR AF: 0.209

Gnomad ASJ AF: 0.217

Gnomad EAS AF: 0.0564

Gnomad SAS AF: 0.169

Gnomad FIN AF: 0.295

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.308

Gnomad OTH AF: 0.243

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

GnomAD4 genome AF: 0.243 AC: 36901 AN: 152068 Hom.: 4880 Cov.: 31 AF XY: 0.238 AC XY: 17682 AN XY: 74334

Gnomad4 AFR AF: 0.170

Gnomad4 AMR AF: 0.209

Gnomad4 ASJ AF: 0.217

Gnomad4 EAS AF: 0.0566

Gnomad4 SAS AF: 0.169

Gnomad4 FIN AF: 0.295

Gnomad4 NFE AF: 0.308

Gnomad4 OTH AF: 0.245

Alfa AF: 0.265 Hom.: 934

Bravo AF: 0.232

Asia WGS AF: 0.137 AC: 478 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.2
DANN	Benign	0.64

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs13431652; hg19: chr2-169753415;