Variant 4-7654128-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_020777.3(SORCS2):c.814-6C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.688 in 1,567,860 control chromosomes in the GnomAD database, including 383,421 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.57 ( 29196 hom., cov: 34)

Exomes 𝑓: 0.70 ( 354225 hom. )

Consequence

SORCS2
NM_020777.3 splice_region, intron

Scores

Splicing: ADA: 0.0001637

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.673

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 made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.861 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SORCS2	NM_020777.3 link	c.814-6C>T		splice_region_variant, intron_variant		ENST00000507866.6	NP_065828.2	Q96PQ0

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
SORCS2	ENST00000507866.6 link	c.814-6C>T	splice_region_variant, intron_variant	1	NM_020777.3	ENSP00000422185.2	Q96PQ0
SORCS2	ENST00000329016.10 link	c.298-6C>T	splice_region_variant, intron_variant	5			B5MED8
SORCS2	ENST00000511199.1 link	n.429-6C>T	splice_region_variant, intron_variant	4

Frequencies

GnomAD3 genomes

AF:

0.570

AC:

86720

AN:

152014

Hom.:

29180

Cov.:

show subpopulations

Gnomad AFR

AF:

0.187

Gnomad AMI

AF:

0.714

Gnomad AMR

AF:

0.687

Gnomad ASJ

AF:

0.681

Gnomad EAS

AF:

0.883

Gnomad SAS

AF:

0.609

Gnomad FIN

AF:

0.747

Gnomad MID

AF:

0.639

Gnomad NFE

AF:

0.715

Gnomad OTH

AF:

0.588

GnomAD3 exomes

AF:

0.664

AC:

122284

AN:

184260

Hom.:

42788

AF XY:

0.662

AC XY:

64676

AN XY:

97704

show subpopulations

Gnomad AFR exome

AF:

0.160

Gnomad AMR exome

AF:

0.736

Gnomad ASJ exome

AF:

0.670

Gnomad EAS exome

AF:

0.878

Gnomad SAS exome

AF:

0.597

Gnomad FIN exome

AF:

0.733

Gnomad NFE exome

AF:

0.685

Gnomad OTH exome

AF:

0.674

GnomAD4 exome

AF:

0.701

AC:

991835

AN:

1415728

Hom.:

354225

Cov.:

AF XY:

0.698

AC XY:

488388

AN XY:

699840

show subpopulations

Gnomad4 AFR exome

AF:

0.165

Gnomad4 AMR exome

AF:

0.728

Gnomad4 ASJ exome

AF:

0.668

Gnomad4 EAS exome

AF:

0.866

Gnomad4 SAS exome

AF:

0.606

Gnomad4 FIN exome

AF:

0.736

Gnomad4 NFE exome

AF:

0.718

Gnomad4 OTH exome

AF:

0.675

GnomAD4 genome

AF:

0.570

AC:

86743

AN:

152132

Hom.:

29196

Cov.:

AF XY:

0.575

AC XY:

42773

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.187

Gnomad4 AMR

AF:

0.687

Gnomad4 ASJ

AF:

0.681

Gnomad4 EAS

AF:

0.883

Gnomad4 SAS

AF:

0.611

Gnomad4 FIN

AF:

0.747

Gnomad4 NFE

AF:

0.715

Gnomad4 OTH

AF:

0.592

Alfa

AF:

0.674

Hom.:

58879

Bravo

AF:

0.553

Asia WGS

AF:

0.704

AC:

2448

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

7.0

DANN

Benign

0.46

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00016

dbscSNV1_RF

Benign

0.010

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over