rs871938

Variant names:

• chr4-7564822-G-T
• rs871938
• NM_020777.3:c.648+33193G>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SORCS2	NM_020777.3	c.648+33193G>T		intron_variant	Intron 3 of 26	ENST00000507866.6	NP_065828.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SORCS2	ENST00000507866.6	c.648+33193G>T		intron_variant	Intron 3 of 26	1	NM_020777.3	ENSP00000422185.2
SORCS2	ENST00000511199.1	n.263+33193G>T		intron_variant	Intron 3 of 5	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

African (AFR) AF: 0.266 AC: 11043 AN: 41512

American (AMR) AF: 0.678 AC: 10368 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.667 AC: 2311 AN: 3466

East Asian (EAS) AF: 0.894 AC: 4633 AN: 5184

South Asian (SAS) AF: 0.775 AC: 3736 AN: 4822

European-Finnish (FIN) AF: 0.704 AC: 7450 AN: 10582

Middle Eastern (MID) AF: 0.656 AC: 193 AN: 294

European-Non Finnish (NFE) AF: 0.658 AC: 44693 AN: 67972

Other (OTH) AF: 0.579 AC: 1223 AN: 2112

Alfa AF: 0.644 Hom.: 19093

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
PhyloP100		0.075
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs871938; hg19: chr4-7566549;