12-100311134-GCC-TCA

Variant names:

• chr12-100311134-GCC-TCA
• NM_017988.6:c.571_573delGCCinsTCA
• SCYL2 p.Ala191Ser

Variant summary

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

The NM_017988.6(SCYL2):​c.571_573delGCCinsTCA​(p.Ala191Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. 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. A191T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SCYL2 NM_017988.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.73
• 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 0 ACMG points.

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.571_573delGCCinsTCA	p.Ala191Ser	missense	N/A	NP_060458.3
	SCYL2	NM_001330253.2		c.571_573delGCCinsTCA	p.Ala191Ser	missense	N/A	NP_001317182.1	A0A0U1RQQ9
	SCYL2	NM_001330254.2		c.571_573delGCCinsTCA	p.Ala191Ser	missense	N/A	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.571_573delGCCinsTCA	p.Ala191Ser	missense	N/A	ENSP00000354061.2	Q6P3W7
	SCYL2	ENST00000930683.1		c.571_573delGCCinsTCA	p.Ala191Ser	missense	N/A	ENSP00000600742.1
	SCYL2	ENST00000635101.1	TSL:5	c.571_573delGCCinsTCA	p.Ala191Ser	missense	N/A	ENSP00000489123.1	A0A0U1RQQ9

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		6.7

Splicing

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: chr12-100704912;