SCYL2 p.Gly177Arg

Variant names:

• chr12-100311092-G-C
• NM_017988.6:c.529G>C
• SCYL2 p.Gly177Arg

Your query was ambiguous. Multiple possible variants found:

• chr12-100311092-G-C
• chr12-100311092-G-A
• chr12-100311092-GGA-CGT
• chr12-100311092-GGA-CGC
• chr12-100311092-GGA-CGG
• chr12-100311092-GGA-AGG

Variant summary

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

The NM_017988.6(SCYL2):​c.529G>C​(p.Gly177Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SCYL2 NM_017988.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.07
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• arthrogryposis multiplex congenita 4, neurogenic, with agenesis of the corpus callosum

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: PanelApp Australia, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017988.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCYL2	NM_017988.6	MANE Select	c.529G>C	p.Gly177Arg	missense	Exon 5 of 18	NP_060458.3
	SCYL2	NM_001330253.2		c.529G>C	p.Gly177Arg	missense	Exon 5 of 19	NP_001317182.1	A0A0U1RQQ9
	SCYL2	NM_001330254.2		c.529G>C	p.Gly177Arg	missense	Exon 5 of 19	NP_001317183.1	A0A0U1RQQ9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCYL2	ENST00000360820.7	TSL:1 MANE Select	c.529G>C	p.Gly177Arg	missense	Exon 5 of 18	ENSP00000354061.2	Q6P3W7
	SCYL2	ENST00000930683.1		c.529G>C	p.Gly177Arg	missense	Exon 5 of 19	ENSP00000600742.1
	SCYL2	ENST00000635101.1	TSL:5	c.529G>C	p.Gly177Arg	missense	Exon 5 of 19	ENSP00000489123.1	A0A0U1RQQ9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.76
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Uncertain	0.13
CADD	Uncertain	24
DANN	Benign	0.86
DEOGEN2	Benign	0.0020	T
Eigen	Benign	-0.069
Eigen_PC	Benign	0.16
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.012	T
MetaRNN	Uncertain	0.46	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-0.72	N
PhyloP100		8.1
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	0.16	N
REVEL	Benign	0.29
Sift	Benign	0.43	T
Sift4G	Benign	0.54	T
Varity_R		0.27
gMVP		0.86
Mutation Taster		=45/55	disease causing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr12-100704870;