2-63914230-G-A

Variant names:

• chr2-63914230-G-A
• rs1558987428
• NM_016516.3:c.2286C>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_016516.3(VPS54):​c.2286C>T​(p.Ile762Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: VPS54 NM_016516.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.49
• Publications: 0 publications found

Genes affected

VPS54 (HGNC:18652): (VPS54 subunit of GARP complex) This gene encodes for a protein that in yeast forms part of a trimeric vacuolar-protein-sorting complex that is required for retrograde transport of proteins from prevacuoles to the late Golgi compartment. As in yeast, mammalian Vps54 proteins contain a coiled-coil region and dileucine motifs. Alternative splicing results in multiple transcript variants encoding different isoforms [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP7: Synonymous conserved (PhyloP=3.49 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016516.3. 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
	VPS54	NM_016516.3	MANE Select	c.2286C>T	p.Ile762Ile	synonymous	Exon 17 of 23	NP_057600.2	Q9P1Q0-1
	VPS54	NM_001005739.2		c.2250C>T	p.Ile750Ile	synonymous	Exon 17 of 23	NP_001005739.1	Q9P1Q0-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VPS54	ENST00000272322.9	TSL:5 MANE Select	c.2286C>T	p.Ile762Ile	synonymous	Exon 17 of 23	ENSP00000272322.4	Q9P1Q0-1
	VPS54	ENST00000409558.8	TSL:1	c.2250C>T	p.Ile750Ile	synonymous	Exon 17 of 23	ENSP00000386980.3	Q9P1Q0-4
	VPS54	ENST00000354504.7	TSL:1	c.1827C>T	p.Ile609Ile	synonymous	Exon 14 of 20	ENSP00000346499.3	Q9P1Q0-3

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
BayesDel_noAF	Benign	-0.45
CADD	Benign	8.3
DANN	Benign	0.68
PhyloP100		3.5
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs1558987428; hg19: chr2-64141364;