chr20-2860242-AAGAGTGGACCCGTGG-GAGAGC

Position:

• chr20-2860242-AAGAGTGGACCCGTGG-GAGAGC

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_022575.4(VPS16):​c.244_259delinsGAGAGC​(p.Lys82GlufsTer126) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: VPS16 NM_022575.4 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 8.58

Genes affected

VPS16 (HGNC:14584): (VPS16 core subunit of CORVET and HOPS complexes) Vesicle mediated protein sorting plays an important role in segregation of intracellular molecules into distinct organelles. Genetic studies in yeast have identified more than 40 vacuolar protein sorting (VPS) genes involved in vesicle transport to vacuoles. This gene encodes the human homolog of yeast class C Vps16 protein. The mammalian class C Vps proteins are predominantly associated with late endosomes/lysosomes, and like their yeast counterparts, may mediate vesicle trafficking steps in the endosome/lysosome pathway. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2009]

ACMG classification

Verdict is Pathogenic. Variant got 11 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 20-2860242-AAGAGTGGACCCGTGG-GAGAGC is Pathogenic according to our data. Variant chr20-2860242-AAGAGTGGACCCGTGG-GAGAGC is described in ClinVar as [Pathogenic]. Clinvar id is 1065417.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VPS16	NM_022575.4	c.244_259delinsGAGAGC	p.Lys82GlufsTer126	frameshift_variant	4/24	ENST00000380445.8	NP_072097.2
VPS16	NM_080413.3	c.244_259delinsGAGAGC	p.Lys82GlufsTer126	frameshift_variant	4/20		NP_536338.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VPS16	ENST00000380445.8	c.244_259delinsGAGAGC	p.Lys82GlufsTer126	frameshift_variant	4/24	1	NM_022575.4	ENSP00000369810	P1
VPS16	ENST00000380469.7	c.244_259delinsGAGAGC	p.Lys82GlufsTer126	frameshift_variant	4/20	2		ENSP00000369836
VPS16	ENST00000417508.1	c.16-207_16-192delinsGAGAGC		intron_variant		5		ENSP00000409840
VPS16	ENST00000453689.5	c.16-207_16-192delinsGAGAGC		intron_variant		3		ENSP00000417031

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

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Dystonia 30 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Oct 20, 2021

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-2840888;