rs12500759

chr4-7708153-C-T

Variant summary

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

The NM_020777.3(SORCS2):c.1868+3869C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.252 in 152,148 control chromosomes in the GnomAD database, including 5,169 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 (5169 hom., cov: 33)
• Consequence: SORCS2 NM_020777.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.05

Genes affected

SORCS2 (HGNC:16698): (sortilin related VPS10 domain containing receptor 2) This gene encodes one family member of vacuolar protein sorting 10 (VPS10) domain-containing receptor proteins. The VPS10 domain name comes from the yeast carboxypeptidase Y sorting receptor Vps10 protein. Members of this gene family are large with many exons but the CDS lengths are usually less than 3700 nt. Very large introns typically separate the exons encoding the VPS10 domain; the remaining exons are separated by much smaller-sized introns. These genes are strongly expressed in the central nervous system. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.324 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SORCS2	NM_020777.3	c.1868+3869C>T		intron_variant		ENST00000507866.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SORCS2	ENST00000507866.6	c.1868+3869C>T		intron_variant		1	NM_020777.3	P1

Frequencies

GnomAD3 genomes AF: 0.252 AC: 38342 AN: 152030 Hom.: 5167 Cov.: 33

Gnomad AFR AF: 0.146

Gnomad AMI AF: 0.210

Gnomad AMR AF: 0.246

Gnomad ASJ AF: 0.300

Gnomad EAS AF: 0.335

Gnomad SAS AF: 0.289

Gnomad FIN AF: 0.294

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.302

Gnomad OTH AF: 0.237

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

GnomAD4 genome AF: 0.252 AC: 38360 AN: 152148 Hom.: 5169 Cov.: 33 AF XY: 0.253 AC XY: 18784 AN XY: 74392

Gnomad4 AFR AF: 0.145

Gnomad4 AMR AF: 0.246

Gnomad4 ASJ AF: 0.300

Gnomad4 EAS AF: 0.337

Gnomad4 SAS AF: 0.290

Gnomad4 FIN AF: 0.294

Gnomad4 NFE AF: 0.302

Gnomad4 OTH AF: 0.233

Alfa AF: 0.288 Hom.: 8536

Bravo AF: 0.242

Asia WGS AF: 0.269 AC: 937 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	3.9
Dann	Benign	0.55

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: rs12500759; hg19: chr4-7709880;