rs871938

chr4-7564822-G-T

Variant summary

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

The NM_020777.3(SORCS2):c.648+33193G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.568 in 152,154 control chromosomes in the GnomAD database, including 27,366 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 0.57 (27366 hom., cov: 33)
• Consequence: SORCS2 NM_020777.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0750

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.872 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SORCS2	NM_020777.3	c.648+33193G>T		intron_variant		ENST00000507866.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SORCS2	ENST00000507866.6	c.648+33193G>T		intron_variant		1	NM_020777.3	P1
SORCS2	ENST00000511199.1	n.263+33193G>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.568 AC: 86318 AN: 152036 Hom.: 27353 Cov.: 33

Gnomad AFR AF: 0.266

Gnomad AMI AF: 0.771

Gnomad AMR AF: 0.677

Gnomad ASJ AF: 0.667

Gnomad EAS AF: 0.894

Gnomad SAS AF: 0.774

Gnomad FIN AF: 0.704

Gnomad MID AF: 0.652

Gnomad NFE AF: 0.658

Gnomad OTH AF: 0.575

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

GnomAD4 genome AF: 0.568 AC: 86350 AN: 152154 Hom.: 27366 Cov.: 33 AF XY: 0.577 AC XY: 42904 AN XY: 74386

Gnomad4 AFR AF: 0.266

Gnomad4 AMR AF: 0.678

Gnomad4 ASJ AF: 0.667

Gnomad4 EAS AF: 0.894

Gnomad4 SAS AF: 0.775

Gnomad4 FIN AF: 0.704

Gnomad4 NFE AF: 0.658

Gnomad4 OTH AF: 0.579

Alfa AF: 0.647 Hom.: 17405

Bravo AF: 0.549

Asia WGS AF: 0.780 AC: 2709 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	2.3
Dann	Benign	0.61

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: rs871938; hg19: chr4-7566549;