rs568758

Positions:

• chr11-74970364-A-G

Variant summary

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

The NM_014752.3(SPCS2):​c.494+665A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.405 in 152,020 control chromosomes in the GnomAD database, including 13,285 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 0.40 (13285 hom., cov: 32)
• Consequence: SPCS2 NM_014752.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.108

Genes affected

SPCS2 (HGNC:28962): (signal peptidase complex subunit 2) Predicted to enable peptidase activity. Predicted to be involved in protein targeting to ER and signal peptide processing. Predicted to be located in endoplasmic reticulum membrane. Predicted to be part of signal peptidase complex. [provided by Alliance of Genome Resources, Apr 2022]

SPCS2 (HGNC:):

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 = 0.49 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPCS2	NM_014752.3	c.494+665A>G		intron_variant		ENST00000263672.11	NP_055567.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPCS2	ENST00000263672.11	c.494+665A>G		intron_variant		1	NM_014752.3	ENSP00000263672.6

Frequencies

GnomAD3 genomes AF: 0.405 AC: 61504 AN: 151902 Hom.: 13290 Cov.: 32

Gnomad AFR AF: 0.283

Gnomad AMI AF: 0.607

Gnomad AMR AF: 0.326

Gnomad ASJ AF: 0.449

Gnomad EAS AF: 0.199

Gnomad SAS AF: 0.477

Gnomad FIN AF: 0.449

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.494

Gnomad OTH AF: 0.435

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

GnomAD4 genome AF: 0.405 AC: 61510 AN: 152020 Hom.: 13285 Cov.: 32 AF XY: 0.401 AC XY: 29808 AN XY: 74308

Gnomad4 AFR AF: 0.282

Gnomad4 AMR AF: 0.325

Gnomad4 ASJ AF: 0.449

Gnomad4 EAS AF: 0.199

Gnomad4 SAS AF: 0.477

Gnomad4 FIN AF: 0.449

Gnomad4 NFE AF: 0.494

Gnomad4 OTH AF: 0.433

Alfa AF: 0.447 Hom.: 2296

Bravo AF: 0.386

Asia WGS AF: 0.340 AC: 1181 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.93
DANN	Benign	0.74

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs568758; hg19: chr11-74681409;