rs2394522

Positions:

• chr10-69152515-G-C
• chr10-69152515-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004896.5(VPS26A):​c.154-3297G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 152,010 control chromosomes in the GnomAD database, including 2,777 homozygotes. 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: 𝑓 0.18 (2777 hom., cov: 31)
• Consequence: VPS26A NM_004896.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.324

Genes affected

VPS26A (HGNC:12711): (VPS26 retromer complex component A) This gene belongs to a group of vacuolar protein sorting (VPS) genes. The encoded protein is a component of a large multimeric complex, termed the retromer complex, involved in retrograde transport of proteins from endosomes to the trans-Golgi network. The close structural similarity between the yeast and human proteins that make up this complex suggests a similarity in function. Expression studies in yeast and mammalian cells indicate that this protein interacts directly with VPS35, which serves as the core of the retromer complex. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

VPS26A (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.225 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VPS26A	NM_004896.5	c.154-3297G>C		intron_variant		ENST00000263559.11	NP_004887.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VPS26A	ENST00000263559.11	c.154-3297G>C		intron_variant		1	NM_004896.5	ENSP00000263559.6

Frequencies

GnomAD3 genomes AF: 0.178 AC: 26972 AN: 151892 Hom.: 2771 Cov.: 31

Gnomad AFR AF: 0.100

Gnomad AMI AF: 0.344

Gnomad AMR AF: 0.129

Gnomad ASJ AF: 0.134

Gnomad EAS AF: 0.0347

Gnomad SAS AF: 0.131

Gnomad FIN AF: 0.328

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.228

Gnomad OTH AF: 0.149

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

GnomAD4 genome AF: 0.178 AC: 26982 AN: 152010 Hom.: 2777 Cov.: 31 AF XY: 0.178 AC XY: 13253 AN XY: 74292

Gnomad4 AFR AF: 0.0998

Gnomad4 AMR AF: 0.130

Gnomad4 ASJ AF: 0.134

Gnomad4 EAS AF: 0.0346

Gnomad4 SAS AF: 0.132

Gnomad4 FIN AF: 0.328

Gnomad4 NFE AF: 0.228

Gnomad4 OTH AF: 0.147

Alfa AF: 0.195 Hom.: 396

Bravo AF: 0.159

Asia WGS AF: 0.0840 AC: 292 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.68
DANN	Benign	0.61

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

Other links and lift over

dbSNP: rs2394522; hg19: chr10-70912271;