Genetic Variant SORCS2:p.Gly12Val (chr4-7192681-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_020777.3(SORCS2):c.35G>T(p.Gly12Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000202 in 988,396 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000068 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000012 ( 0 hom. )

Consequence

SORCS2
NM_020777.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.71

Publications

1 publications found

Variant links:

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 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07840535).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020777.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SORCS2	NM_020777.3	MANE Select	c.35G>T	p.Gly12Val	missense	Exon 1 of 27	NP_065828.2	Q96PQ0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SORCS2	ENST00000507866.6	TSL:1 MANE Select	c.35G>T	p.Gly12Val	missense	Exon 1 of 27	ENSP00000422185.2	Q96PQ0

Frequencies

GnomAD3 genomes

AF:

0.00000682

AC:

AN:

146672

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000245

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000119

AC:

AN:

841724

Hom.:

Cov.:

AF XY:

0.00000257

AC XY:

AN XY:

389638

show subpopulations

African (AFR)

AF:

0.0000628

AC:

AN:

15924

American (AMR)

AF:

0.00

AC:

AN:

1290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

5326

East Asian (EAS)

AF:

0.00

AC:

AN:

3862

South Asian (SAS)

AF:

0.00

AC:

AN:

17358

European-Finnish (FIN)

AF:

0.00

AC:

AN:

1100

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1640

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

767464

Other (OTH)

AF:

0.00

AC:

AN:

27760

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000682

AC:

AN:

146672

Hom.:

Cov.:

AF XY:

0.0000140

AC XY:

AN XY:

71358

show subpopulations

African (AFR)

AF:

0.0000245

AC:

AN:

40860

American (AMR)

AF:

0.00

AC:

AN:

14778

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3384

East Asian (EAS)

AF:

0.00

AC:

AN:

5086

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8566

Middle Eastern (MID)

AF:

0.00

AC:

AN:

312

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

65936

Other (OTH)

AF:

0.00

AC:

AN:

2020

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.675

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000151

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.098

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.70

CADD

Benign

(source)

DANN

Benign

0.82

DEOGEN2

Benign

0.0037

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.051

LIST_S2

Benign

0.43

M_CAP

Benign

0.071

MetaRNN

Benign

0.078

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.0

PhyloP100

1.7

PrimateAI

Pathogenic

0.79

PROVEAN

Benign

-0.61

REVEL

Benign

0.019

Sift

Benign

0.32

Sift4G

Benign

0.66

Polyphen

0.032

Vest4

0.11

MutPred

0.27

Loss of catalytic residue at G12 (P = 0.0269)

MVP

0.63

MPC

2.2

ClinPred

0.080

GERP RS

1.5

PromoterAI

-0.11

Neutral

(source)

Varity_R

0.065

gMVP

0.12

Mutation Taster

=93/7

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over