Genetic Variant SORCS2:p.Pro31_Ser33dup (chr4-7192725-C-CCGCCGCGCT) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM4

The NM_020777.3(SORCS2):c.92_100dupCGCGCTCGC(p.Pro31_Ser33dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000224 in 990,650 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00024 ( 0 hom. )

Consequence

SORCS2
NM_020777.3 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.356

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 2 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_020777.3.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SORCS2	NM_020777.3 link	c.92_100dupCGCGCTCGC	p.Pro31_Ser33dup	disruptive_inframe_insertion	Exon 1 of 27	ENST00000507866.6	NP_065828.2	Q96PQ0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SORCS2	ENST00000507866.6 link	c.92_100dupCGCGCTCGC	p.Pro31_Ser33dup	disruptive_inframe_insertion	Exon 1 of 27	1	NM_020777.3	ENSP00000422185.2		Q96PQ0

Frequencies

GnomAD3 genomes

AF:

0.000116

AC:

AN:

146386

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000678

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000118

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000228

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000243

AC:

205

AN:

844264

Hom.:

Cov.:

AF XY:

0.000240

AC XY:

AN XY:

391176

show subpopulations

African (AFR)

AF:

0.000188

AC:

AN:

15956

American (AMR)

AF:

0.00

AC:

AN:

1366

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

5360

East Asian (EAS)

AF:

0.000252

AC:

AN:

3964

South Asian (SAS)

AF:

0.000115

AC:

AN:

17400

European-Finnish (FIN)

AF:

0.00

AC:

AN:

1358

Middle Eastern (MID)

AF:

0.00182

AC:

AN:

1652

European-Non Finnish (NFE)

AF:

0.000246

AC:

189

AN:

769294

Other (OTH)

AF:

0.000251

AC:

AN:

27914

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.446

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000116

AC:

AN:

146386

Hom.:

Cov.:

AF XY:

0.0000562

AC XY:

AN XY:

71214

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

40814

American (AMR)

AF:

0.0000678

AC:

AN:

14742

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3386

East Asian (EAS)

AF:

0.00

AC:

AN:

5090

South Asian (SAS)

AF:

0.00

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.000118

AC:

AN:

8444

Middle Eastern (MID)

AF:

0.00

AC:

AN:

308

European-Non Finnish (NFE)

AF:

0.000228

AC:

AN:

65854

Other (OTH)

AF:

0.00

AC:

AN:

2020

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000214

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Sep 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.36

Mutation Taster

=86/14

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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4-7192725-C-CCGCCGCGCT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over