dbSNP rs7965910: SCYL2:c.177+35C>A (chr12-100283182-C-A) – ACMG Classification: Benign (-20 pts)

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

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]

SCYL2 links:

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
SCYL2	NM_017988.6 link	c.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
SCYL2	ENST00000360820.7 link	c.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.:

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.:

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.:

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over