4-7717522-T-G

Position:

• chr4-7717522-T-G

Variant summary

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

The NM_020777.3(SORCS2):​c.2253-490T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.973 in 152,312 control chromosomes in the GnomAD database, including 72,176 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 0.97 (72176 hom., cov: 33)
• Consequence: SORCS2 NM_020777.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.02

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]

SORCS2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SORCS2	NM_020777.3	c.2253-490T>G		intron_variant		ENST00000507866.6	NP_065828.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SORCS2	ENST00000507866.6	c.2253-490T>G		intron_variant		1	NM_020777.3	ENSP00000422185.2
SORCS2	ENST00000329016.10	c.1737-490T>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.973 AC: 148058 AN: 152194 Hom.: 72147 Cov.: 33

Gnomad AFR AF: 0.908

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.987

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.999

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.994

Gnomad NFE AF: 0.999

Gnomad OTH AF: 0.979

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

GnomAD4 genome AF: 0.973 AC: 148138 AN: 152312 Hom.: 72176 Cov.: 33 AF XY: 0.973 AC XY: 72464 AN XY: 74468

Gnomad4 AFR AF: 0.907

Gnomad4 AMR AF: 0.987

Gnomad4 ASJ AF: 1.00

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.999

Gnomad4 FIN AF: 1.00

Gnomad4 NFE AF: 0.999

Gnomad4 OTH AF: 0.980

Alfa AF: 0.984 Hom.: 10490

Bravo AF: 0.969

Asia WGS AF: 0.993 AC: 3453 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.8
DANN	Benign	0.34

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs6446618; hg19: chr4-7719249;