rs7965910

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_017988.6(SCYL2):​c.177+35C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 1,530,252 control chromosomes in the GnomAD database, including 32,322 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.22 ( 4337 hom., cov: 32)
Exomes 𝑓: 0.20 ( 27985 hom. )

Consequence

SCYL2
NM_017988.6 intron

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.35
Variant links:
Genes affected
SCYL2 (HGNC:19286): (SCY1 like pseudokinase 2) The protein encoded by this gene associates with clathrin-coated complexes at the plasma membrane and with endocytic coated vesicles. The encoded protein phosphorylates the beta2 subunit of the plasma membrane adapter complex AP2 and interacts with clathrin, showing involvement in clathrin-dependent pathways between the trans-Golgi network and the endosomal system. In addition, this protein has a role in the Wnt signaling pathway by targeting frizzled 5 (Fzd5) for lysosomal degradation. Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Dec 2015]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.89).
BP6
Variant 12-100283182-C-A is Benign according to our data. Variant chr12-100283182-C-A is described in ClinVar as [Benign]. Clinvar id is 1332927.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.322 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SCYL2NM_017988.6 linkc.177+35C>A intron_variant Intron 2 of 17 ENST00000360820.7 NP_060458.3 Q6P3W7

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SCYL2ENST00000360820.7 linkc.177+35C>A intron_variant Intron 2 of 17 1 NM_017988.6 ENSP00000354061.2 Q6P3W7

Frequencies

GnomAD3 genomes
AF:
0.225
AC:
34121
AN:
151944
Hom.:
4321
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.326
Gnomad AMI
AF:
0.207
Gnomad AMR
AF:
0.191
Gnomad ASJ
AF:
0.208
Gnomad EAS
AF:
0.0408
Gnomad SAS
AF:
0.114
Gnomad FIN
AF:
0.133
Gnomad MID
AF:
0.172
Gnomad NFE
AF:
0.208
Gnomad OTH
AF:
0.222
GnomAD3 exomes
AF:
0.176
AC:
34725
AN:
197368
Hom.:
3553
AF XY:
0.174
AC XY:
18536
AN XY:
106792
show subpopulations
Gnomad AFR exome
AF:
0.331
Gnomad AMR exome
AF:
0.128
Gnomad ASJ exome
AF:
0.199
Gnomad EAS exome
AF:
0.0454
Gnomad SAS exome
AF:
0.119
Gnomad FIN exome
AF:
0.140
Gnomad NFE exome
AF:
0.202
Gnomad OTH exome
AF:
0.181
GnomAD4 exome
AF:
0.196
AC:
270221
AN:
1378190
Hom.:
27985
Cov.:
24
AF XY:
0.194
AC XY:
132265
AN XY:
681926
show subpopulations
Gnomad4 AFR exome
AF:
0.327
Gnomad4 AMR exome
AF:
0.135
Gnomad4 ASJ exome
AF:
0.195
Gnomad4 EAS exome
AF:
0.0455
Gnomad4 SAS exome
AF:
0.119
Gnomad4 FIN exome
AF:
0.138
Gnomad4 NFE exome
AF:
0.208
Gnomad4 OTH exome
AF:
0.191
GnomAD4 genome
AF:
0.225
AC:
34188
AN:
152062
Hom.:
4337
Cov.:
32
AF XY:
0.218
AC XY:
16169
AN XY:
74340
show subpopulations
Gnomad4 AFR
AF:
0.327
Gnomad4 AMR
AF:
0.191
Gnomad4 ASJ
AF:
0.208
Gnomad4 EAS
AF:
0.0407
Gnomad4 SAS
AF:
0.115
Gnomad4 FIN
AF:
0.133
Gnomad4 NFE
AF:
0.208
Gnomad4 OTH
AF:
0.225
Alfa
AF:
0.205
Hom.:
4635
Bravo
AF:
0.234
Asia WGS
AF:
0.112
AC:
390
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:1
-
Breakthrough Genomics, Breakthrough Genomics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

Arthrogryposis multiplex congenita 4, neurogenic, with agenesis of the corpus callosum Benign:1
Jul 15, 2021
Genome-Nilou Lab
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.89
CADD
Benign
2.4
DANN
Benign
0.24

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

LitVar

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

Other links and lift over

dbSNP: rs7965910; hg19: chr12-100676960; API