rs1018394834

Variant names:

• chr4-7192696-C-A
• rs1018394834
• NM_020777.3:c.50C>A

Your query was ambiguous. Multiple possible variants found:

• chr4-7192696-C-A
• chr4-7192696-C-G
• chr4-7192696-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020777.3(SORCS2):​c.50C>A​(p.Ala17Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000119 in 842,334 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A17G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000012 (0 hom.)
• Consequence: SORCS2 NM_020777.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.248
• Publications: 0 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: 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=0.12044364).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SORCS2	NM_020777.3	c.50C>A	p.Ala17Asp	missense_variant	Exon 1 of 27	ENST00000507866.6	NP_065828.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SORCS2	ENST00000507866.6	c.50C>A	p.Ala17Asp	missense_variant	Exon 1 of 27	1	NM_020777.3	ENSP00000422185.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000119 AC: 1 AN: 842334 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 389996

African (AFR) AF: 0.00 AC: 0 AN: 15928

American (AMR) AF: 0.00 AC: 0 AN: 1310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5340

East Asian (EAS) AF: 0.00 AC: 0 AN: 3884

South Asian (SAS) AF: 0.0000576 AC: 1 AN: 17370

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1162

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1644

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 767910

Other (OTH) AF: 0.00 AC: 0 AN: 27786

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	18
DANN	Benign	0.92
DEOGEN2	Benign	0.0038	T
Eigen	Benign	-0.92
Eigen_PC	Benign	-0.98
FATHMM_MKL	Benign	0.062	N
LIST_S2	Benign	0.33	T
M_CAP	Benign	0.085	D
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.25
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-0.32	N
REVEL	Benign	0.032
Sift	Benign	0.13	T
Sift4G	Benign	0.098	T
Polyphen		0.42	B
Vest4		0.13
MutPred		0.22		Loss of MoRF binding (P = 0.0458);
MVP		0.64
MPC		2.5
ClinPred		0.14	T
GERP RS		1.6
PromoterAI		-0.012	Neutral
Varity_R		0.099
gMVP		0.34
Mutation Taster		=94/6	polymorphism

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: rs1018394834; hg19: chr4-7194423;